De Silva Sumadee, Tennekoon Kamani Hemamala, Dissanayake Aravinda, De Silva Kanishka, Jayasekara Lakshika
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo, 00300, Sri Lanka.
National Cancer Research, Maharagama, Sri Lanka.
Fam Cancer. 2017 Jul;16(3):329-338. doi: 10.1007/s10689-016-9962-9.
Women with breast carcinoma diagnosed before 40 years of age with a strong familial risk have a greater prevalence of germline BRCA1 or BRCA2 variants than late onset breast cancer. Previously germline variants in BRCA1 and BRCA2 genes were characterized in a cohort of Sri Lankan breast cancer patients unselected for age of onset. This study focused on young breast cancer patients who were screened for previously identified hotspot regions in BRCA2 gene. A total of 48 young breast cancer patients with family history of cancer and 25 healthy controls were studied. Direct sequencing was used to detect pathogenic and other sequence variants in the hotspot regions of BRCA2 gene. Thirty-six sequence variants including seven pathogenic (c.2411_2412delAA/p.Glu804Valfs2, c.2500_2501insG/p.Leu834Cysfs4, c.3881T>G/p.Leu1294*, c.4768A>T/p.Lys1590*, c.5645C>G/p.Ser1882*, c.5747delC/p.His1916Phefs*3, c.6728C>T/p.Ser2243Phe) and two likely pathogenic (c.1922C>T and c.3378A>T) variants, two intronic variants of unknown significance (c.1910-74T>C, c.1910-51G>T), two variants of uncertain significance (c.2324C>T c.5104C>T) and 23 benign variants were detected. Among them, seven were novel (pathogenic 5 and likely pathogenic 2). Prevalence of pathogenic and likely pathogenic variants in the hotspots regions of BRCA2 was 23 and 6.3 % respectively in this cohort. This justifies BRCA2 variant testing in young breast cancer patients with family history of cancer in Sri Lanka.
在40岁之前被诊断出患有乳腺癌且具有强烈家族风险的女性，其生殖系BRCA1或BRCA2基因变异的患病率高于晚发性乳腺癌患者。此前，在一组未按发病年龄筛选的斯里兰卡乳腺癌患者中对BRCA1和BRCA2基因的生殖系变异进行了特征分析。本研究聚焦于对BRCA2基因中先前确定的热点区域进行筛查的年轻乳腺癌患者。共研究了48例有癌症家族史的年轻乳腺癌患者和25名健康对照。采用直接测序法检测BRCA2基因热点区域的致病和其他序列变异。检测到36种序列变异，包括7种致病变异（c.2411_2412delAA/p.Glu804Valfs2、c.2500_2501insG/p.Leu834Cysfs4、c.3881T>G/p.Leu1294*、c.4768A>T/p.Lys1590*、c.5645C>G/p.Ser1882*、c.5747delC/p.His1916Phefs*3、c.6728C>T/p.Ser2243Phe）和2种可能致病的变异（c.1922C>T和c.3378A>T）、2种意义未明的内含子变异（c.1910-74T>C、c.1910-51G>T）、2种意义不确定的变异（c.2324C>T、c.5104C>T）以及23种良性变异。其中，7种为新发现的变异（5种致病变异和2种可能致病的变异）。在该队列中，BRCA2基因热点区域致病和可能致病变异的患病率分别为23%和6.3%。这证明在斯里兰卡有癌症家族史的年轻乳腺癌患者中进行BRCA2基因变异检测是合理的。
