Three novel BRCA1/BRCA2 mutations in breast/ovarian cancer families in Croatia

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• 作者：Sonja Levanat^a ; ^{levanat@irb.hr} ; Vesna Musani^a ; Mirela Levacic Cvok^b ; Ilona Susac^c ; Maja Sabol^a ; Petar Ozretic^a ; Diana Car^a ; Domagoj Eljuga^d ; Ljerka Eljuga^c ; Damir Eljuga^e
• 关键词：BRCA1 ; BRCA2 ; hereditary breast/ovarian cancer ; high-resolution melting analysis ; quantitative multiplex PCR of short fluorescent fragments
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：1 May, 2012
• 卷：498
• 期：2
• 页码：169-176
• 文件大小：645 K

摘要

BRCA1 and BRCA2 genes from 167 candidates (145 families) were scanned for mutations. We identified 14 pathogenic point mutations in 17 candidates, 9 in BRCA1 and 5 in BRCA2. Of those, 11 have been previously described and 3 were novel (c.5335C > T in BRCA1 and c.4139_4140dupTT and c.8175G > A in BRCA2). No large deletions or duplications involving BRCA1 and BRCA2 genes were identified. No founder mutations were detected for the Croatian population. Croatia shares most of the mutations with neighboring Slovenia and also with Germany, Austria and Poland.

Two common sequence variants in BRCA1, c.2077G > A and c.4956G > A, were found more frequently in mutation carriers compared to healthy controls. No difference in BRCA2 variants was detected between the groups.

Haplotype inference showed no difference in haplotype distributions between deleterious mutation carriers and non-carriers in neither BRCA1 nor BRCA2. In silico analyses identified one BRCA1 sequence variant (c.4039A > G) and two BRCA2 variants (c.5986G > A and c.6884G > C) as harmful with high probability, and inconclusive results were obtained for our novel BRCA2 variant c.3864_3866delTAA.

Combination of QMPSF and HRMA methods provides high detection rate and complete coverage of BRCA1/2 genes. Benefit of BRCA1/2 mutation testing is clear, since we detected mutations in young unaffected women, who will be closely monitored for breast and ovarian cancer.