Abstract 2597: Identification of new genes for hereditary breast cancer
| Autor: | Svetlana N. Abysheva, Evgeny N. Suspitsin, Evgeny N. Imyanitov, Aglaya G. Iyevleva, Anna P. Sokolenko, Elena V. Chekmariova, Ekaterina Sh Kuligina |
|---|---|
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Cancer Research. 72:2597-2597 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Major hereditary breast cancer (BC) genes, BRCA1 and BRCA2, contribute to no more than 20-25% of familial BC clustering; therefore the majority of BC-predisposing mutations remain to be identified. We have selected for the study 95 BC cases, which showed accumulation of clinical signs of the genetic disease (e.g., occurrence of BC among multiple relatives and/or bilaterality and/or young age at onset), but could not be explained either by BRCA1/2 sequence alterations or by Russian founder mutations in CHEK2 (c.1100delC, c.444+1G>A, del5395) or NBN (657del5) genes. The entire coding regions of DNA repair genes were examined using high resolution melting (HRM) analysis and DNA sequencing. Three of 16 genes selected for the study (CHEK2, NBN, PALB2, BRIP1, BARD1, RAD51C, BLM, FANCG, CHEK1, PARP1, PARP2, ERCC1, XPE, BRD7, RNF8, RAD51A) contained potentially deleterious mutations. Two patients carried inactivating lesion in the PALB2 gene (p.R414X and p.Q921X); both these carriers had the bilateral form of BC disease. 1 woman harbored mutation in the FANCG gene (c.520_524delTCTAinsC), which resulted in the loss of serine at position 174 and lysine to glutamine substitution at position 175. The analysis of the BLM gene revealed two heterozygous carriers of the c.1642 C>T (Q548X) allele. This mutation was subjected to the extended study, which confirmed its recurrent character and strong association with BC risk: BLM c.1642 C>T (Q548X) heterozygotes were detected in 17/1,498 (1.1%) BC patients as compared to 2/1,093 (0.2%) healthy females (p = 0.004). As expected for BC-predisposing gene, the BLM 1670 C>T allele tended to be associated with first-degree family history of BC, early onset and bilateral appearance of the disease. This is the first demonstration of the role of the BLM heterozygosity in the determination of BC risk. The impact of constitutional BLM mutations in hereditary cancer predisposition deserves to be tested in other ethnic groups as well as in other tumor types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2597. doi:1538-7445.AM2012-2597 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|