Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases
Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western popu...
Ausführliche Beschreibung
Autor*in: |
Yosr Hamdi [verfasserIn] Maroua Boujemaa [verfasserIn] Mariem Ben Rekaya [verfasserIn] Cherif Ben Hamda [verfasserIn] Najah Mighri [verfasserIn] Houda El Benna [verfasserIn] Nesrine Mejri [verfasserIn] Soumaya Labidi [verfasserIn] Nouha Daoud [verfasserIn] Chokri Naouali [verfasserIn] Olfa Messaoud [verfasserIn] Mariem Chargui [verfasserIn] Kais Ghedira [verfasserIn] Mohamed Samir Boubaker [verfasserIn] Ridha Mrad [verfasserIn] Hamouda Boussen [verfasserIn] Sonia Abdelhak [verfasserIn] the PEC Consortium [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2018 |
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Übergeordnetes Werk: |
In: Journal of Translational Medicine - BMC, 2003, 16(2018), 1, Seite 13 |
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Übergeordnetes Werk: |
volume:16 ; year:2018 ; number:1 ; pages:13 |
Links: |
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DOI / URN: |
10.1186/s12967-018-1504-9 |
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Katalog-ID: |
DOAJ076398994 |
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520 | |a Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. | ||
650 | 4 | |a Breast cancer | |
650 | 4 | |a Exome sequencing | |
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10.1186/s12967-018-1504-9 doi (DE-627)DOAJ076398994 (DE-599)DOAJ4aaf76a9dd8f4e0988e7dafd8f4a7f72 DE-627 ger DE-627 rakwb eng Yosr Hamdi verfasserin aut Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families Medicine R Maroua Boujemaa verfasserin aut Mariem Ben Rekaya verfasserin aut Cherif Ben Hamda verfasserin aut Najah Mighri verfasserin aut Houda El Benna verfasserin aut Nesrine Mejri verfasserin aut Soumaya Labidi verfasserin aut Nouha Daoud verfasserin aut Chokri Naouali verfasserin aut Olfa Messaoud verfasserin aut Mariem Chargui verfasserin aut Kais Ghedira verfasserin aut Mohamed Samir Boubaker verfasserin aut Ridha Mrad verfasserin aut Hamouda Boussen verfasserin aut Sonia Abdelhak verfasserin aut the PEC Consortium verfasserin aut In Journal of Translational Medicine BMC, 2003 16(2018), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:16 year:2018 number:1 pages:13 https://doi.org/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/article/4aaf76a9dd8f4e0988e7dafd8f4a7f72 kostenfrei http://link.springer.com/article/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 16 2018 1 13 |
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10.1186/s12967-018-1504-9 doi (DE-627)DOAJ076398994 (DE-599)DOAJ4aaf76a9dd8f4e0988e7dafd8f4a7f72 DE-627 ger DE-627 rakwb eng Yosr Hamdi verfasserin aut Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families Medicine R Maroua Boujemaa verfasserin aut Mariem Ben Rekaya verfasserin aut Cherif Ben Hamda verfasserin aut Najah Mighri verfasserin aut Houda El Benna verfasserin aut Nesrine Mejri verfasserin aut Soumaya Labidi verfasserin aut Nouha Daoud verfasserin aut Chokri Naouali verfasserin aut Olfa Messaoud verfasserin aut Mariem Chargui verfasserin aut Kais Ghedira verfasserin aut Mohamed Samir Boubaker verfasserin aut Ridha Mrad verfasserin aut Hamouda Boussen verfasserin aut Sonia Abdelhak verfasserin aut the PEC Consortium verfasserin aut In Journal of Translational Medicine BMC, 2003 16(2018), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:16 year:2018 number:1 pages:13 https://doi.org/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/article/4aaf76a9dd8f4e0988e7dafd8f4a7f72 kostenfrei http://link.springer.com/article/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 16 2018 1 13 |
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10.1186/s12967-018-1504-9 doi (DE-627)DOAJ076398994 (DE-599)DOAJ4aaf76a9dd8f4e0988e7dafd8f4a7f72 DE-627 ger DE-627 rakwb eng Yosr Hamdi verfasserin aut Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families Medicine R Maroua Boujemaa verfasserin aut Mariem Ben Rekaya verfasserin aut Cherif Ben Hamda verfasserin aut Najah Mighri verfasserin aut Houda El Benna verfasserin aut Nesrine Mejri verfasserin aut Soumaya Labidi verfasserin aut Nouha Daoud verfasserin aut Chokri Naouali verfasserin aut Olfa Messaoud verfasserin aut Mariem Chargui verfasserin aut Kais Ghedira verfasserin aut Mohamed Samir Boubaker verfasserin aut Ridha Mrad verfasserin aut Hamouda Boussen verfasserin aut Sonia Abdelhak verfasserin aut the PEC Consortium verfasserin aut In Journal of Translational Medicine BMC, 2003 16(2018), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:16 year:2018 number:1 pages:13 https://doi.org/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/article/4aaf76a9dd8f4e0988e7dafd8f4a7f72 kostenfrei http://link.springer.com/article/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 16 2018 1 13 |
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10.1186/s12967-018-1504-9 doi (DE-627)DOAJ076398994 (DE-599)DOAJ4aaf76a9dd8f4e0988e7dafd8f4a7f72 DE-627 ger DE-627 rakwb eng Yosr Hamdi verfasserin aut Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families Medicine R Maroua Boujemaa verfasserin aut Mariem Ben Rekaya verfasserin aut Cherif Ben Hamda verfasserin aut Najah Mighri verfasserin aut Houda El Benna verfasserin aut Nesrine Mejri verfasserin aut Soumaya Labidi verfasserin aut Nouha Daoud verfasserin aut Chokri Naouali verfasserin aut Olfa Messaoud verfasserin aut Mariem Chargui verfasserin aut Kais Ghedira verfasserin aut Mohamed Samir Boubaker verfasserin aut Ridha Mrad verfasserin aut Hamouda Boussen verfasserin aut Sonia Abdelhak verfasserin aut the PEC Consortium verfasserin aut In Journal of Translational Medicine BMC, 2003 16(2018), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:16 year:2018 number:1 pages:13 https://doi.org/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/article/4aaf76a9dd8f4e0988e7dafd8f4a7f72 kostenfrei http://link.springer.com/article/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 16 2018 1 13 |
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10.1186/s12967-018-1504-9 doi (DE-627)DOAJ076398994 (DE-599)DOAJ4aaf76a9dd8f4e0988e7dafd8f4a7f72 DE-627 ger DE-627 rakwb eng Yosr Hamdi verfasserin aut Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families Medicine R Maroua Boujemaa verfasserin aut Mariem Ben Rekaya verfasserin aut Cherif Ben Hamda verfasserin aut Najah Mighri verfasserin aut Houda El Benna verfasserin aut Nesrine Mejri verfasserin aut Soumaya Labidi verfasserin aut Nouha Daoud verfasserin aut Chokri Naouali verfasserin aut Olfa Messaoud verfasserin aut Mariem Chargui verfasserin aut Kais Ghedira verfasserin aut Mohamed Samir Boubaker verfasserin aut Ridha Mrad verfasserin aut Hamouda Boussen verfasserin aut Sonia Abdelhak verfasserin aut the PEC Consortium verfasserin aut In Journal of Translational Medicine BMC, 2003 16(2018), 1, Seite 13 (DE-627)369084136 (DE-600)2118570-0 14795876 nnns volume:16 year:2018 number:1 pages:13 https://doi.org/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/article/4aaf76a9dd8f4e0988e7dafd8f4a7f72 kostenfrei http://link.springer.com/article/10.1186/s12967-018-1504-9 kostenfrei https://doaj.org/toc/1479-5876 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 16 2018 1 13 |
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Yosr Hamdi @@aut@@ Maroua Boujemaa @@aut@@ Mariem Ben Rekaya @@aut@@ Cherif Ben Hamda @@aut@@ Najah Mighri @@aut@@ Houda El Benna @@aut@@ Nesrine Mejri @@aut@@ Soumaya Labidi @@aut@@ Nouha Daoud @@aut@@ Chokri Naouali @@aut@@ Olfa Messaoud @@aut@@ Mariem Chargui @@aut@@ Kais Ghedira @@aut@@ Mohamed Samir Boubaker @@aut@@ Ridha Mrad @@aut@@ Hamouda Boussen @@aut@@ Sonia Abdelhak @@aut@@ the PEC Consortium @@aut@@ |
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Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. 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Yosr Hamdi Maroua Boujemaa Mariem Ben Rekaya Cherif Ben Hamda Najah Mighri Houda El Benna Nesrine Mejri Soumaya Labidi Nouha Daoud Chokri Naouali Olfa Messaoud Mariem Chargui Kais Ghedira Mohamed Samir Boubaker Ridha Mrad Hamouda Boussen Sonia Abdelhak the PEC Consortium |
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family specific genetic predisposition to breast cancer: results from tunisian whole exome sequenced breast cancer cases |
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Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases |
abstract |
Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. |
abstractGer |
Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. |
abstract_unstemmed |
Abstract Background A family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking. Methods A whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein–protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk. Results Sequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein–protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6. Conclusions In this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific. |
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Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases |
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https://doi.org/10.1186/s12967-018-1504-9 https://doaj.org/article/4aaf76a9dd8f4e0988e7dafd8f4a7f72 http://link.springer.com/article/10.1186/s12967-018-1504-9 https://doaj.org/toc/1479-5876 |
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Maroua Boujemaa Mariem Ben Rekaya Cherif Ben Hamda Najah Mighri Houda El Benna Nesrine Mejri Soumaya Labidi Nouha Daoud Chokri Naouali Olfa Messaoud Mariem Chargui Kais Ghedira Mohamed Samir Boubaker Ridha Mrad Hamouda Boussen Sonia Abdelhak the PEC Consortium |
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