High prevalence and breast cancer predisposing role of the BLMc.1642 C>T (Q548X) mutation in Russia

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Item Type:	Article
Title:	High prevalence and breast cancer predisposing role of the BLMc.1642 C>T (Q548X) mutation in Russia
Creators Name:	Sokolenko, A.P., Iyevleva, A.G., Preobrazhenskaya, E.V., Mitiushkina, N.V., Abysheva, S.N., Suspitsin, E.N., Kuligina, E.S., Gorodnova, T.V., Pfeifer, W., Togo, A.V., Turkevich, E.A., Ivantsov, A.O., Voskresenskiy, D.V., Dolmatov, G.D., Bit-Sava, E.M., Matsko, D.E., Semiglazov, V.F., Fichtner, I., Larionov, A.A., Kuznetsov, S.G., Antoniou, A.C. and Imyanitov, E.N.
Abstract:	The BLM gene belongs to the RecQ helicase family and has been implicated in the maintenance of genomic stability. Its homozygous germline inactivation causes Bloom syndrome, a severe genetic disorder characterized by growth retardation, impaired fertility and highly elevated cancer risk. We hypothesized that BLM is a candidate gene for breast cancer (BC) predisposition. Sequencing of its entire coding region in 95 genetically enriched Russian BC patients identified 2 heterozygous carriers of the c.1642 C>T (Q548X) mutation. The extended study revealed this allele in 17/1498 (1.1%) breast cancer (BC) cases vs. 2/1093 (0.2%) healthy women (p = 0.004). There was a suggestion that BLM mutations were more common in patients reporting first-degree family history of BC (6/251 (2.4%) vs. 11/1247 (0.9%), p = 0.05), early-onset cases (12/762 (1.6%) vs. 5/736 (0.7%), p = 0.14), and women with bilateral appearance of the disease (2/122 (1.6%) vs. 15/1376 (1.1%), p = 0.64). None of the BLM-associated BC exhibited somatic loss of heterozygosity at the BLM gene locus. This study demonstrates that BLM Q548X allele is recurrent in Slavic subjects and may be associated with breast cancer risk.
Keywords:	BLM, Bloom Syndrome, Breast Cancer, BRCA1, Loss of Heterozygosity
Source:	International Journal of Cancer
ISSN:	0020-7136
Publisher:	Wiley-Blackwell
Volume:	130
Number:	12
Page Range:	2867-2873
Date:	15 June 2012
Official Publication:	https://doi.org/10.1002/ijc.26342
PubMed:	View item in PubMed

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