copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.

<h4>Background</h4>Inherited factors predisposing individuals to breast and ovarian cancer are largely unidentified in a majority of families with hereditary breast and ovarian cancer (HBOC). We aimed to identify germline copy number variations (CNVs) contributing to HBOC susceptibility...

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Autores principales:	Kirsi M Kuusisto, Oyediran Akinrinade, Mauno Vihinen, Minna Kankuri-Tammilehto, Satu-Leena Laasanen, Johanna Schleutker
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4842ef037dbe436a9fc91a1bc1c7d1af
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spelling	oai:doaj.org-article:4842ef037dbe436a9fc91a1bc1c7d1af2021-11-18T08:59:51Zcopy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.1932-620310.1371/journal.pone.0071802https://doaj.org/article/4842ef037dbe436a9fc91a1bc1c7d1af2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23967248/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Inherited factors predisposing individuals to breast and ovarian cancer are largely unidentified in a majority of families with hereditary breast and ovarian cancer (HBOC). We aimed to identify germline copy number variations (CNVs) contributing to HBOC susceptibility in the Finnish population.<h4>Methods</h4>A cohort of 84 HBOC individuals (negative for BRCA1/2-founder mutations and pre-screened for the most common breast cancer genes) and 36 healthy controls were analysed with a genome-wide SNP array. CNV-affecting genes were further studied by Gene Ontology term enrichment, pathway analyses, and database searches to reveal genes with potential for breast and ovarian cancer predisposition. CNVs that were considered to be important were validated and genotyped in 20 additional HBOC individuals (6 CNVs) and in additional healthy controls (5 CNVs) by qPCR.<h4>Results</h4>An intronic deletion in the EPHA3 receptor tyrosine kinase was enriched in HBOC individuals (12 of 101, 11.9%) compared with controls (27 of 432, 6.3%) (OR = 1.96; P = 0.055). EPHA3 was identified in several enriched molecular functions including receptor activity. Both a novel intronic deletion in the CSMD1 tumor suppressor gene and a homozygous intergenic deletion at 5q15 were identified in 1 of 101 (1.0%) HBOC individuals but were very rare (1 of 436, 0.2% and 1 of 899, 0.1%, respectively) in healthy controls suggesting that these variants confer disease susceptibility.<h4>Conclusion</h4>This study reveals new information regarding the germline CNVs that likely contribute to HBOC susceptibility in Finland. This information may be used to facilitate the genetic counselling of HBOC individuals but the preliminary results warrant additional studies of a larger study group.Kirsi M KuusistoOyediran AkinrinadeMauno VihinenMinna Kankuri-TammilehtoSatu-Leena LaasanenJohanna SchleutkerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71802 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kirsi M Kuusisto Oyediran Akinrinade Mauno Vihinen Minna Kankuri-Tammilehto Satu-Leena Laasanen Johanna Schleutker copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.
description	<h4>Background</h4>Inherited factors predisposing individuals to breast and ovarian cancer are largely unidentified in a majority of families with hereditary breast and ovarian cancer (HBOC). We aimed to identify germline copy number variations (CNVs) contributing to HBOC susceptibility in the Finnish population.<h4>Methods</h4>A cohort of 84 HBOC individuals (negative for BRCA1/2-founder mutations and pre-screened for the most common breast cancer genes) and 36 healthy controls were analysed with a genome-wide SNP array. CNV-affecting genes were further studied by Gene Ontology term enrichment, pathway analyses, and database searches to reveal genes with potential for breast and ovarian cancer predisposition. CNVs that were considered to be important were validated and genotyped in 20 additional HBOC individuals (6 CNVs) and in additional healthy controls (5 CNVs) by qPCR.<h4>Results</h4>An intronic deletion in the EPHA3 receptor tyrosine kinase was enriched in HBOC individuals (12 of 101, 11.9%) compared with controls (27 of 432, 6.3%) (OR = 1.96; P = 0.055). EPHA3 was identified in several enriched molecular functions including receptor activity. Both a novel intronic deletion in the CSMD1 tumor suppressor gene and a homozygous intergenic deletion at 5q15 were identified in 1 of 101 (1.0%) HBOC individuals but were very rare (1 of 436, 0.2% and 1 of 899, 0.1%, respectively) in healthy controls suggesting that these variants confer disease susceptibility.<h4>Conclusion</h4>This study reveals new information regarding the germline CNVs that likely contribute to HBOC susceptibility in Finland. This information may be used to facilitate the genetic counselling of HBOC individuals but the preliminary results warrant additional studies of a larger study group.
format	article
author	Kirsi M Kuusisto Oyediran Akinrinade Mauno Vihinen Minna Kankuri-Tammilehto Satu-Leena Laasanen Johanna Schleutker
author_facet	Kirsi M Kuusisto Oyediran Akinrinade Mauno Vihinen Minna Kankuri-Tammilehto Satu-Leena Laasanen Johanna Schleutker
author_sort	Kirsi M Kuusisto
title	copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.
title_short	copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.
title_full	copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.
title_fullStr	copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.
title_full_unstemmed	copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.
title_sort	copy number variation analysis in familial brca1/2-negative finnish breast and ovarian cancer.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4842ef037dbe436a9fc91a1bc1c7d1af
work_keys_str_mv	AT kirsimkuusisto copynumbervariationanalysisinfamilialbrca12negativefinnishbreastandovariancancer AT oyediranakinrinade copynumbervariationanalysisinfamilialbrca12negativefinnishbreastandovariancancer AT maunovihinen copynumbervariationanalysisinfamilialbrca12negativefinnishbreastandovariancancer AT minnakankuritammilehto copynumbervariationanalysisinfamilialbrca12negativefinnishbreastandovariancancer AT satuleenalaasanen copynumbervariationanalysisinfamilialbrca12negativefinnishbreastandovariancancer AT johannaschleutker copynumbervariationanalysisinfamilialbrca12negativefinnishbreastandovariancancer
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copy number variation analysis in familial BRCA1/2-negative Finnish breast and ovarian cancer.

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