BRCA1 and BRCA2 germline mutations in Moroccan breast/ovarian cancer families: Novel mutations and unclassified variants

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• 作者：Amal Tazzite^a ; ¹ ; Hassan Jouhadi^b ; ¹ ; Sellama Nadifi^a ; ^{labgenmed@yahoo.fr} ; Paolo Aretini^c ; Elisabetta Falaschi^c ; Anita Collavoli^c ; Abdellatif Benider^b ; Maria Adelaide Caligo^c
• 关键词：Breast cancer ; BRCA1 ; BRCA2 ; Germline mutations ; Morocco
• 刊名：Gynecologic Oncology
• 出版年：2012
• 期刊代码：295_00908258
• 类别：med
• 出版时间：June, 2012
• 卷：125
• 期：3
• 页码：687-692
• 文件大小：298 K

摘要

Objective

Breast cancer is the most common female cancer in Morocco. About 5 to 10%are due to hereditary predisposition and mutations in m>BRCA1m> and m>BRCA2m> genes are responsible for an important proportion of high-risk breast/ovarian cancer families. The relevance of m>BRCA1m>/2 mutations in the Moroccan population was not studied. The main objective of this study is to investigate the spectrum of m>BRCA1m> and m>BRCA2m> germline mutations in early onset and familial breast/ovarian cancer among Moroccan women.

Methods

We screened the entire coding sequences and intron/exon boundaries of m>BRCA1m> and m>BRCA2m> genes in 40 patients by direct sequencing.

Results

Nine pathogenic mutations were detected in ten unrelated families, five deleterious mutations in m>BRCA1m> gene and four mutations in m>BRCA2m> gene. Four novel mutations were found: one in m>BRCA1m> (c.2805delA/2924delA) and three in m>BRCA2m> (c.3381delT/3609delT; c.7110delA/7338delA and c.7235insG/7463insG). We also identified 51 distinct polymorphisms and unclassified variants (three described for the first time).

Conclusions

Our data suggest that m>BRCA1m> and m>BRCA2m> mutations are responsible for a significant proportion of familial breast cancer in Moroccan patients. Therefore full m>BRCA1m>/2 screening should be offered to patients with a family history of breast/ovarian cancer.