To characterize the spectrum of BRCA1 and BRCA2 pathogenic germline variants in women from south-west Poland and west Ukraine affected with breast or ovarian cancer. Testing in women at high risk of breast and ovarian cancer in these regions is currently mainly limited to founder mutations.

Unrelated women affected with breast and/or ovarian cancer from Poland (n = 337) and Ukraine (n = 123) were screened by targeted sequencing. Excluded from targeted sequencing were 34 Polish women who had previously been identified as carrying a founder mutation in BRCA1. No prior testing had been conducted among the Ukrainian women. Thus, this study screened BRCA1 and BRCA2 in the germline DNA of 426 women in total.

We identified 31 and 18 women as carriers of pathogenic/likely pathogenic (P/LP) genetic variants in BRCA1 and BRCA2, respectively. We observed five BRCA1 and eight BRCA2 P/LP variants (13/337, 3.9%) in the Polish women. Combined with the 34/337 (10.1%) founder variants identified prior to this study, the overall P/LP variant frequency in the Polish women was thus 14% (47/337). Among the Ukrainian women, 16/123 (13%) women were identified as carrying a founder mutation and 20/123 (16.3%) were found to carry non-founder P/LP variants (10 in BRCA1 and 10 in BRCA2).

These results indicate that genetic testing in women at high risk of breast and ovarian cancer in Poland and Ukraine should not be limited to founder mutations. Extended testing will enhance risk stratification and management for these women and their families.

为了表征患有乳腺癌或卵巢癌的波兰西南波兰和乌克兰西部妇女的BRCA1和BRCA2致病种系变异谱。在这些地区中，乳腺癌和卵巢癌高风险女性的检测目前主要限于创始人突变。

通过靶向测序筛选了波兰（n = 337）和乌克兰（n = 123）患有乳腺癌和/或卵巢癌的无关女性。从靶向测序中排除了34名波兰妇女，这些妇女先前被鉴定为在BRCA1中携带创始人突变。乌克兰妇女之前未进行过测试。因此，本研究共筛选了426名女性生殖系DNA中的BRCA1和BRCA2。

我们确定了31和18名妇女分别为BRCA1和BRCA2中的致病性/可能致病性（P / LP）遗传变异的携带者。我们在波兰妇女中观察到5个BRCA1和8个BRCA2 P / LP变异体（13 / 337，3.9％）。结合本研究之前确定的34/337（10.1％）创始人变异，波兰妇女的整体P / LP变异频率因此为14％（47/337）。在乌克兰妇女中，有16/123（13％）名妇女被确定具有创始人突变，而20/123（16.3％）被发现具有非创始人P / LP变异（BRCA1中为10，BRCA2中为10 ）。

这些结果表明，在波兰和乌克兰，对乳腺癌和卵巢癌高危女性进行基因检测不应仅限于创始人突变。扩展测试将增强这些妇女及其家庭的风险分层和管理。