Szwiec M, Jakubowska A, Górski B, Huzarski T, Tomiczek-Szwiec J, Gronwald J, Dębniak T, Byrski T, Kluźniak W, Wokołorczyk D, Birkenfeld B, Akbari M R, Narod S A, Lubiński J, Cybulski C
Department of Clinical Oncology, Tadeusz Koszarowski Regional Oncology Center, Opole, Poland.
Clin Genet. 2015 Mar;87(3):288-92. doi: 10.1111/cge.12360. Epub 2014 Mar 12.
Three founder alleles of BRCA1 (C61G, 4153delA, 5382insC) were reported in Poland in 2000, and these three mutations have comprised the standard testing panel used throughout the country. However, since 2000, other recurrent mutations of BRCA1 and BRCA2 have been reported. To establish if the inclusion of one or more of these mutations will increase the sensitivity of the standard test panel, we studied 1164 Polish women with unselected breast cancer diagnosed at age of 50 or below. All women were genotyped for 12 recurrent mutations of BRCA1 and BRCA2. We identified a mutation in 83 of 1164 patients (7.1%) including 61 women with one of the original three mutations (C61G, 4153delA, 5382insC) and 22 women with a different mutation (1.9%). Three new mutations (3819del5, 185delAG and 5370C>T) were seen in multiple families. By including these three mutations in the extended panel, the mutant frequency increased from 5.2 to 6.7%. Polish women with breast cancer diagnosed at age of 50 or below should be screened with a panel of six founder mutations of BRCA1 (C61G, 4153delA, 5382insC, 3819del5, 185delAG and 5370C>T).
2000年在波兰报道了BRCA1的三个始祖等位基因（C61G、4153delA、5382insC），这三个突变构成了全国使用的标准检测组合。然而，自2000年以来，已报道了BRCA1和BRCA2的其他复发性突变。为了确定纳入这些突变中的一个或多个是否会提高标准检测组合的敏感性，我们研究了1164名年龄在50岁及以下、未经选择的乳腺癌波兰女性。所有女性均对BRCA1和BRCA2的12个复发性突变进行了基因分型。我们在1164名患者中的83名（7.1%）中发现了突变，其中61名女性携带最初三个突变之一（C61G、4153delA、5382insC），22名女性携带不同的突变（1.9%）。在多个家族中发现了三个新突变（3819del5、185delAG和5370C>T）。通过在扩展组合中纳入这三个突变，突变频率从5.2%增加到了6.7%。年龄在50岁及以下的波兰乳腺癌女性应使用包含BRCA1的六个始祖突变（C61G、4153delA、5382insC、3819del5、185delAG和5370C>T）的组合进行筛查。
