High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma
Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes f...
Ausführliche Beschreibung
Autor*in: |
Catarina Campos [verfasserIn] Sofia Fragoso [verfasserIn] Rafael Luís [verfasserIn] Filipe Pinto [verfasserIn] Cheila Brito [verfasserIn] Susana Esteves [verfasserIn] Margarida Pataco [verfasserIn] Sidónia Santos [verfasserIn] Patrícia Machado [verfasserIn] João B. Vicente [verfasserIn] Joaninha Costa Rosa [verfasserIn] Branca M. Cavaco [verfasserIn] Cecília Moura [verfasserIn] Marta Pojo [verfasserIn] |
---|
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2020 |
---|
Schlagwörter: |
---|
Übergeordnetes Werk: |
In: Genes - MDPI AG, 2010, 11(2020), 4, p 403 |
---|---|
Übergeordnetes Werk: |
volume:11 ; year:2020 ; number:4, p 403 |
Links: |
---|
DOI / URN: |
10.3390/genes11040403 |
---|
Katalog-ID: |
DOAJ002568926 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | DOAJ002568926 | ||
003 | DE-627 | ||
005 | 20240413000336.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230225s2020 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/genes11040403 |2 doi | |
035 | |a (DE-627)DOAJ002568926 | ||
035 | |a (DE-599)DOAJ75c7b15645d143f397b431736acb3a28 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
050 | 0 | |a QH426-470 | |
100 | 0 | |a Catarina Campos |e verfasserin |4 aut | |
245 | 1 | 0 | |a High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma |
264 | 1 | |c 2020 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
520 | |a Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. | ||
650 | 4 | |a cutaneous melanoma | |
650 | 4 | |a germline mutations | |
650 | 4 | |a WES | |
650 | 4 | |a hereditary melanoma | |
653 | 0 | |a Genetics | |
700 | 0 | |a Sofia Fragoso |e verfasserin |4 aut | |
700 | 0 | |a Rafael Luís |e verfasserin |4 aut | |
700 | 0 | |a Filipe Pinto |e verfasserin |4 aut | |
700 | 0 | |a Cheila Brito |e verfasserin |4 aut | |
700 | 0 | |a Susana Esteves |e verfasserin |4 aut | |
700 | 0 | |a Margarida Pataco |e verfasserin |4 aut | |
700 | 0 | |a Sidónia Santos |e verfasserin |4 aut | |
700 | 0 | |a Patrícia Machado |e verfasserin |4 aut | |
700 | 0 | |a João B. Vicente |e verfasserin |4 aut | |
700 | 0 | |a Joaninha Costa Rosa |e verfasserin |4 aut | |
700 | 0 | |a Branca M. Cavaco |e verfasserin |4 aut | |
700 | 0 | |a Cecília Moura |e verfasserin |4 aut | |
700 | 0 | |a Marta Pojo |e verfasserin |4 aut | |
773 | 0 | 8 | |i In |t Genes |d MDPI AG, 2010 |g 11(2020), 4, p 403 |w (DE-627)614096537 |w (DE-600)2527218-4 |x 20734425 |7 nnns |
773 | 1 | 8 | |g volume:11 |g year:2020 |g number:4, p 403 |
856 | 4 | 0 | |u https://doi.org/10.3390/genes11040403 |z kostenfrei |
856 | 4 | 0 | |u https://doaj.org/article/75c7b15645d143f397b431736acb3a28 |z kostenfrei |
856 | 4 | 0 | |u https://www.mdpi.com/2073-4425/11/4/403 |z kostenfrei |
856 | 4 | 2 | |u https://doaj.org/toc/2073-4425 |y Journal toc |z kostenfrei |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_DOAJ | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 11 |j 2020 |e 4, p 403 |
author_variant |
c c cc s f sf r l rl f p fp c b cb s e se m p mp s s ss p m pm j b v jbv j c r jcr b m c bmc c m cm m p mp |
---|---|
matchkey_str |
article:20734425:2020----::ihhogpteunigdniisnvlucpiiiyeef |
hierarchy_sort_str |
2020 |
callnumber-subject-code |
QH |
publishDate |
2020 |
allfields |
10.3390/genes11040403 doi (DE-627)DOAJ002568926 (DE-599)DOAJ75c7b15645d143f397b431736acb3a28 DE-627 ger DE-627 rakwb eng QH426-470 Catarina Campos verfasserin aut High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. cutaneous melanoma germline mutations WES hereditary melanoma Genetics Sofia Fragoso verfasserin aut Rafael Luís verfasserin aut Filipe Pinto verfasserin aut Cheila Brito verfasserin aut Susana Esteves verfasserin aut Margarida Pataco verfasserin aut Sidónia Santos verfasserin aut Patrícia Machado verfasserin aut João B. Vicente verfasserin aut Joaninha Costa Rosa verfasserin aut Branca M. Cavaco verfasserin aut Cecília Moura verfasserin aut Marta Pojo verfasserin aut In Genes MDPI AG, 2010 11(2020), 4, p 403 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:11 year:2020 number:4, p 403 https://doi.org/10.3390/genes11040403 kostenfrei https://doaj.org/article/75c7b15645d143f397b431736acb3a28 kostenfrei https://www.mdpi.com/2073-4425/11/4/403 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 4, p 403 |
spelling |
10.3390/genes11040403 doi (DE-627)DOAJ002568926 (DE-599)DOAJ75c7b15645d143f397b431736acb3a28 DE-627 ger DE-627 rakwb eng QH426-470 Catarina Campos verfasserin aut High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. cutaneous melanoma germline mutations WES hereditary melanoma Genetics Sofia Fragoso verfasserin aut Rafael Luís verfasserin aut Filipe Pinto verfasserin aut Cheila Brito verfasserin aut Susana Esteves verfasserin aut Margarida Pataco verfasserin aut Sidónia Santos verfasserin aut Patrícia Machado verfasserin aut João B. Vicente verfasserin aut Joaninha Costa Rosa verfasserin aut Branca M. Cavaco verfasserin aut Cecília Moura verfasserin aut Marta Pojo verfasserin aut In Genes MDPI AG, 2010 11(2020), 4, p 403 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:11 year:2020 number:4, p 403 https://doi.org/10.3390/genes11040403 kostenfrei https://doaj.org/article/75c7b15645d143f397b431736acb3a28 kostenfrei https://www.mdpi.com/2073-4425/11/4/403 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 4, p 403 |
allfields_unstemmed |
10.3390/genes11040403 doi (DE-627)DOAJ002568926 (DE-599)DOAJ75c7b15645d143f397b431736acb3a28 DE-627 ger DE-627 rakwb eng QH426-470 Catarina Campos verfasserin aut High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. cutaneous melanoma germline mutations WES hereditary melanoma Genetics Sofia Fragoso verfasserin aut Rafael Luís verfasserin aut Filipe Pinto verfasserin aut Cheila Brito verfasserin aut Susana Esteves verfasserin aut Margarida Pataco verfasserin aut Sidónia Santos verfasserin aut Patrícia Machado verfasserin aut João B. Vicente verfasserin aut Joaninha Costa Rosa verfasserin aut Branca M. Cavaco verfasserin aut Cecília Moura verfasserin aut Marta Pojo verfasserin aut In Genes MDPI AG, 2010 11(2020), 4, p 403 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:11 year:2020 number:4, p 403 https://doi.org/10.3390/genes11040403 kostenfrei https://doaj.org/article/75c7b15645d143f397b431736acb3a28 kostenfrei https://www.mdpi.com/2073-4425/11/4/403 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 4, p 403 |
allfieldsGer |
10.3390/genes11040403 doi (DE-627)DOAJ002568926 (DE-599)DOAJ75c7b15645d143f397b431736acb3a28 DE-627 ger DE-627 rakwb eng QH426-470 Catarina Campos verfasserin aut High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. cutaneous melanoma germline mutations WES hereditary melanoma Genetics Sofia Fragoso verfasserin aut Rafael Luís verfasserin aut Filipe Pinto verfasserin aut Cheila Brito verfasserin aut Susana Esteves verfasserin aut Margarida Pataco verfasserin aut Sidónia Santos verfasserin aut Patrícia Machado verfasserin aut João B. Vicente verfasserin aut Joaninha Costa Rosa verfasserin aut Branca M. Cavaco verfasserin aut Cecília Moura verfasserin aut Marta Pojo verfasserin aut In Genes MDPI AG, 2010 11(2020), 4, p 403 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:11 year:2020 number:4, p 403 https://doi.org/10.3390/genes11040403 kostenfrei https://doaj.org/article/75c7b15645d143f397b431736acb3a28 kostenfrei https://www.mdpi.com/2073-4425/11/4/403 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 4, p 403 |
allfieldsSound |
10.3390/genes11040403 doi (DE-627)DOAJ002568926 (DE-599)DOAJ75c7b15645d143f397b431736acb3a28 DE-627 ger DE-627 rakwb eng QH426-470 Catarina Campos verfasserin aut High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. cutaneous melanoma germline mutations WES hereditary melanoma Genetics Sofia Fragoso verfasserin aut Rafael Luís verfasserin aut Filipe Pinto verfasserin aut Cheila Brito verfasserin aut Susana Esteves verfasserin aut Margarida Pataco verfasserin aut Sidónia Santos verfasserin aut Patrícia Machado verfasserin aut João B. Vicente verfasserin aut Joaninha Costa Rosa verfasserin aut Branca M. Cavaco verfasserin aut Cecília Moura verfasserin aut Marta Pojo verfasserin aut In Genes MDPI AG, 2010 11(2020), 4, p 403 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:11 year:2020 number:4, p 403 https://doi.org/10.3390/genes11040403 kostenfrei https://doaj.org/article/75c7b15645d143f397b431736acb3a28 kostenfrei https://www.mdpi.com/2073-4425/11/4/403 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020 4, p 403 |
language |
English |
source |
In Genes 11(2020), 4, p 403 volume:11 year:2020 number:4, p 403 |
sourceStr |
In Genes 11(2020), 4, p 403 volume:11 year:2020 number:4, p 403 |
format_phy_str_mv |
Article |
institution |
findex.gbv.de |
topic_facet |
cutaneous melanoma germline mutations WES hereditary melanoma Genetics |
isfreeaccess_bool |
true |
container_title |
Genes |
authorswithroles_txt_mv |
Catarina Campos @@aut@@ Sofia Fragoso @@aut@@ Rafael Luís @@aut@@ Filipe Pinto @@aut@@ Cheila Brito @@aut@@ Susana Esteves @@aut@@ Margarida Pataco @@aut@@ Sidónia Santos @@aut@@ Patrícia Machado @@aut@@ João B. Vicente @@aut@@ Joaninha Costa Rosa @@aut@@ Branca M. Cavaco @@aut@@ Cecília Moura @@aut@@ Marta Pojo @@aut@@ |
publishDateDaySort_date |
2020-01-01T00:00:00Z |
hierarchy_top_id |
614096537 |
id |
DOAJ002568926 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ002568926</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240413000336.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230225s2020 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3390/genes11040403</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ002568926</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ75c7b15645d143f397b431736acb3a28</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Catarina Campos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">cutaneous melanoma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">germline mutations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">WES</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">hereditary melanoma</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sofia Fragoso</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rafael Luís</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Filipe Pinto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cheila Brito</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Susana Esteves</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Margarida Pataco</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sidónia Santos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Patrícia Machado</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">João B. Vicente</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Joaninha Costa Rosa</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Branca M. Cavaco</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cecília Moura</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marta Pojo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Genes</subfield><subfield code="d">MDPI AG, 2010</subfield><subfield code="g">11(2020), 4, p 403</subfield><subfield code="w">(DE-627)614096537</subfield><subfield code="w">(DE-600)2527218-4</subfield><subfield code="x">20734425</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:11</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:4, p 403</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3390/genes11040403</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/75c7b15645d143f397b431736acb3a28</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.mdpi.com/2073-4425/11/4/403</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2073-4425</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">11</subfield><subfield code="j">2020</subfield><subfield code="e">4, p 403</subfield></datafield></record></collection>
|
callnumber-first |
Q - Science |
author |
Catarina Campos |
spellingShingle |
Catarina Campos misc QH426-470 misc cutaneous melanoma misc germline mutations misc WES misc hereditary melanoma misc Genetics High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma |
authorStr |
Catarina Campos |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)614096537 |
format |
electronic Article |
delete_txt_mv |
keep |
author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
collection |
DOAJ |
remote_str |
true |
callnumber-label |
QH426-470 |
illustrated |
Not Illustrated |
issn |
20734425 |
topic_title |
QH426-470 High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma cutaneous melanoma germline mutations WES hereditary melanoma |
topic |
misc QH426-470 misc cutaneous melanoma misc germline mutations misc WES misc hereditary melanoma misc Genetics |
topic_unstemmed |
misc QH426-470 misc cutaneous melanoma misc germline mutations misc WES misc hereditary melanoma misc Genetics |
topic_browse |
misc QH426-470 misc cutaneous melanoma misc germline mutations misc WES misc hereditary melanoma misc Genetics |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
cr |
hierarchy_parent_title |
Genes |
hierarchy_parent_id |
614096537 |
hierarchy_top_title |
Genes |
isfreeaccess_txt |
true |
familylinks_str_mv |
(DE-627)614096537 (DE-600)2527218-4 |
title |
High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma |
ctrlnum |
(DE-627)DOAJ002568926 (DE-599)DOAJ75c7b15645d143f397b431736acb3a28 |
title_full |
High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma |
author_sort |
Catarina Campos |
journal |
Genes |
journalStr |
Genes |
callnumber-first-code |
Q |
lang_code |
eng |
isOA_bool |
true |
recordtype |
marc |
publishDateSort |
2020 |
contenttype_str_mv |
txt |
author_browse |
Catarina Campos Sofia Fragoso Rafael Luís Filipe Pinto Cheila Brito Susana Esteves Margarida Pataco Sidónia Santos Patrícia Machado João B. Vicente Joaninha Costa Rosa Branca M. Cavaco Cecília Moura Marta Pojo |
container_volume |
11 |
class |
QH426-470 |
format_se |
Elektronische Aufsätze |
author-letter |
Catarina Campos |
doi_str_mv |
10.3390/genes11040403 |
author2-role |
verfasserin |
title_sort |
high-throughput sequencing identifies 3 novel susceptibility genes for hereditary melanoma |
callnumber |
QH426-470 |
title_auth |
High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma |
abstract |
Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. |
abstractGer |
Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. |
abstract_unstemmed |
Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma. |
collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
container_issue |
4, p 403 |
title_short |
High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma |
url |
https://doi.org/10.3390/genes11040403 https://doaj.org/article/75c7b15645d143f397b431736acb3a28 https://www.mdpi.com/2073-4425/11/4/403 https://doaj.org/toc/2073-4425 |
remote_bool |
true |
author2 |
Sofia Fragoso Rafael Luís Filipe Pinto Cheila Brito Susana Esteves Margarida Pataco Sidónia Santos Patrícia Machado João B. Vicente Joaninha Costa Rosa Branca M. Cavaco Cecília Moura Marta Pojo |
author2Str |
Sofia Fragoso Rafael Luís Filipe Pinto Cheila Brito Susana Esteves Margarida Pataco Sidónia Santos Patrícia Machado João B. Vicente Joaninha Costa Rosa Branca M. Cavaco Cecília Moura Marta Pojo |
ppnlink |
614096537 |
callnumber-subject |
QH - Natural History and Biology |
mediatype_str_mv |
c |
isOA_txt |
true |
hochschulschrift_bool |
false |
doi_str |
10.3390/genes11040403 |
callnumber-a |
QH426-470 |
up_date |
2024-07-04T01:42:05.999Z |
_version_ |
1803610830669873152 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ002568926</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240413000336.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230225s2020 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3390/genes11040403</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ002568926</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ75c7b15645d143f397b431736acb3a28</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH426-470</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Catarina Campos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< were identified as the most promising susceptibility genes in hereditary melanoma. <i<In silico</i< analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of <i<CDH23</i<, <i<ARHGEF40,</i< and <i<BRD9</i< expression in sporadic melanoma by using the TCGA dataset (<i<n</i< = 461). No differences were observed in <i<BRD9</i< expression between melanoma and normal skin samples, nor with melanoma stage, whereas <i<ARHGEF40</i< was found overexpressed, and <i<CDH23</i< was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">cutaneous melanoma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">germline mutations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">WES</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">hereditary melanoma</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sofia Fragoso</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Rafael Luís</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Filipe Pinto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cheila Brito</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Susana Esteves</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Margarida Pataco</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sidónia Santos</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Patrícia Machado</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">João B. Vicente</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Joaninha Costa Rosa</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Branca M. Cavaco</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Cecília Moura</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Marta Pojo</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">Genes</subfield><subfield code="d">MDPI AG, 2010</subfield><subfield code="g">11(2020), 4, p 403</subfield><subfield code="w">(DE-627)614096537</subfield><subfield code="w">(DE-600)2527218-4</subfield><subfield code="x">20734425</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:11</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:4, p 403</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3390/genes11040403</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/75c7b15645d143f397b431736acb3a28</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.mdpi.com/2073-4425/11/4/403</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2073-4425</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">11</subfield><subfield code="j">2020</subfield><subfield code="e">4, p 403</subfield></datafield></record></collection>
|
score |
7.4008045 |