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

N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.
International Journal of Cancer (Impact Factor: 5.09). 06/2012; 130(12):2867-73. DOI: 10.1002/ijc.26342
Source: PubMed


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 two heterozygous carriers of the c.1642 C>T (Q548X) mutation. The extended study revealed this allele in 17/1,498 (1.1%) BC cases vs. 2/1,093 (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. 11/1,247 (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 BC risk.

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    • "Sokolenko et al. [104] have recently revealed a role of BLM gene mutations in hereditary predisposition to breast cancer. This study included 5 patients treated by conventional neoadjuvant therapy; nearly complete pathological response was observed in 3 cases, while the remaining 2 women showed partial reduction of the tumor mass. "
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