van Der Looij M, Wysocka B, Brozek I, Jassem J, Limon J, Olah E
National Institute of Oncology, Department of Molecular Biology, Budapest, Hungary.
Hum Mutat. 2000 May;15(5):480-1. doi: 10.1002/(SICI)1098-1004(200005)15:5<480::AID-HUMU13>3.0.CO;2-G.
Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.
根据所研究的人群不同，BRCA1和BRCA2基因的种系突变在大多数高危乳腺癌/卵巢癌家族中占主导地位。此前，在波兰西部的女性中发现了BRCA1突变。为了进一步明确波兰BRCA1突变谱以及BRCA2突变的影响，我们采用异源双链分析/单链构象多态性联合直接DNA序列分析，对来自波兰东北部的25个高危乳腺癌和/或卵巢癌家族的BRCA1和BRCA2基因所有编码外显子的突变情况进行了分析。在25名先证者中，共有5名（20%）携带3种常见的BRCA1突变（300T>G、3819del5、5382insC）。300T>G突变占BRCA1突变的60%（3/5），等位基因分型表明该突变有一个共同的起源。未发现独特的突变。此外，我们还鉴定出3种BRCA2突变（12%），一种常见的4075delGT，以及两种新的移码突变，7327ins/dupl19和9068delA。我们得出结论，波兰东北部30%的高危家族可能归因于常见的BRCA1突变和独特的BRCA2突变。有趣的是，波兰不同亚区域的BRCA1突变谱似乎有所不同。
