Jasiewicz Andrzej, Rudnicka Helena, Kluźniak Wojciech, Gronwald Wojciech, Kluz Tomasz, Cybulski Cezary, Jakubowska Anna, Lubiński Jan, Gronwald Jacek
Laboratory of Clinical Genetics, Molecular Biology of Cancer and Translational Research, Faculty of Medicine, Rzeszow University, 1a Warzywna St, 35-310, Rzeszów, Poland.
Genetic Counseling Center, Subcarpatian Oncological Hospital, 18 Bielawskiego St, 36-200, Brzozów, Poland.
Hered Cancer Clin Pract. 2022 Apr 5;20(1):12. doi: 10.1186/s13053-022-00219-z.
Mutations in BRCA1 and BRCA2 genes are well-established risk factors of breast and ovarian cancer. In our former study, we observed that approximately 6% of unselected ovarian cancer patients in the region of Podkarpacie (South-East Poland) carry BRCA1 causative founder variants, which is significantly lower than in other regions of Poland. Therefore, it is deeply justified to do research based on the sequencing of whole BRCA1 and BRCA2 genes.
We examined 158 consecutive unselected cases of ovarian cancer patients from the region of Podkarpacie. We performed BRCA1 and BRCA2 genes Next-Generation Sequencing study in all cases.
Altogether, in 18 of 158 (11.4%) ovarian cancer patients with BRCA1 or BRCA2 pathogenic mutations were found. BRCA1 pathogenic variants were detected in 11 of the 158 (7.0%) ovarian cancer cases. 10 of 11 (91%) detected BRCA1 mutations were founder mutations, detectable with the standard test used in Poland. BRCA2 pathogenic variants were found in 7 of the 158 (4.4%) cases. No BRCA2 pathogenic variants were founder mutations. The median age of patients at the diagnosis of the 18 hereditary ovarian cancers was 57.5 years.
The frequency of BRCA1 or BRCA2 gene mutation carriers among patients with ovarian cancer from the Podkarpacie region is comparable to other regions of Poland. However, a significantly higher percentage of BRCA2 gene mutations was observed, that were not detectable with a standard test for detection of founder mutations. Diagnostics based only on testing the BRCA1/2 Polish founder mutations is characterized by relatively low sensitivity in the case of ovarian cancer patients from South-East Poland and should be supplemented by NGS study, in particular of the BRCA2 gene.
BRCA1和BRCA2基因的突变是乳腺癌和卵巢癌公认的风险因素。在我们之前的研究中，我们观察到在Podkarpacie地区（波兰东南部），约6%未经选择的卵巢癌患者携带BRCA1致病的始祖变异，这一比例显著低于波兰其他地区。因此，基于对整个BRCA1和BRCA2基因进行测序开展研究是完全合理的。
我们检查了Podkarpacie地区158例未经选择的连续卵巢癌患者。对所有病例进行了BRCA1和BRCA2基因的二代测序研究。
总共在158例卵巢癌患者中的18例（11.4%）发现了BRCA1或BRCA2致病突变。在158例卵巢癌病例中的11例（7.0%）检测到BRCA1致病变异。在检测到的11例BRCA1突变中有10例（91%）是始祖突变，可通过波兰使用的标准检测方法检测到。在158例病例中的7例（4.4%）发现了BRCA2致病变异。没有BRCA2致病变异是始祖突变。18例遗传性卵巢癌患者诊断时的中位年龄为57.5岁。
Podkarpacie地区卵巢癌患者中BRCA1或BRCA2基因突变携带者的频率与波兰其他地区相当。然而，观察到BRCA2基因突变的比例显著更高，这些突变无法通过检测始祖突变的标准检测方法检测到。对于波兰东南部的卵巢癌患者，仅基于检测BRCA1/2波兰始祖突变的诊断方法灵敏度相对较低，应以二代测序研究作为补充，尤其是对BRCA2基因的研究。
