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 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. Ausführliche Beschreibung

Gespeichert in:

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]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families

Übergeordnetes Werk:	In: Journal of Translational Medicine - BMC, 2003, 16(2018), 1, Seite 13
Übergeordnetes Werk:	volume:16 ; year:2018 ; number:1 ; pages:13

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12967-018-1504-9

Katalog-ID:	DOAJ076398994

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245	1	0	\|a Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases
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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
650		4	\|a Family specific predisposition
650		4	\|a Non BRCA Tunisian families
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700	0		\|a Najah Mighri \|e verfasserin \|4 aut
700	0		\|a Houda El Benna \|e verfasserin \|4 aut
700	0		\|a Nesrine Mejri \|e verfasserin \|4 aut
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700	0		\|a Sonia Abdelhak \|e verfasserin \|4 aut
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allfields	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
spelling	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
allfields_unstemmed	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
allfieldsGer	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
allfieldsSound	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
language	English
source	In Journal of Translational Medicine 16(2018), 1, Seite 13 volume:16 year:2018 number:1 pages:13
sourceStr	In Journal of Translational Medicine 16(2018), 1, Seite 13 volume:16 year:2018 number:1 pages:13
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families Medicine R
isfreeaccess_bool	true
container_title	Journal of Translational Medicine
authorswithroles_txt_mv	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@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	369084136
id	DOAJ076398994
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">DOAJ076398994</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230309143014.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230228s2018 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12967-018-1504-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ076398994</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ4aaf76a9dd8f4e0988e7dafd8f4a7f72</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="100" ind1="0" ind2=" "><subfield code="a">Yosr Hamdi</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</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">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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Breast cancer</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Exome sequencing</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Family specific predisposition</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Non BRCA Tunisian families</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">R</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Maroua Boujemaa</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Mariem Ben Rekaya</subfield><subfield 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author	Yosr Hamdi
spellingShingle	Yosr Hamdi misc Breast cancer misc Exome sequencing misc Family specific predisposition misc Non BRCA Tunisian families misc Medicine misc R Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases
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topic_title	Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases Breast cancer Exome sequencing Family specific predisposition Non BRCA Tunisian families
topic	misc Breast cancer misc Exome sequencing misc Family specific predisposition misc Non BRCA Tunisian families misc Medicine misc R
topic_unstemmed	misc Breast cancer misc Exome sequencing misc Family specific predisposition misc Non BRCA Tunisian families misc Medicine misc R
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title	Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases
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title_full	Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases
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author_browse	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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title_sort	family specific genetic predisposition to breast cancer: results from tunisian whole exome sequenced breast cancer cases
title_auth	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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title_short	Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases
url	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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author2	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
author2Str	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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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. 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Family specific genetic predisposition to breast cancer: results from Tunisian whole exome sequenced breast cancer cases

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