Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.     

合并肺癌的多原发恶性肿瘤70例临床病理特征分析北大核心

目的:探讨合并肺癌的多原发恶性肿瘤(multiple primary malignancies,MPM)患者临床病理特征。方法:收集2017年01月01日至2019年12月31日陕西省肿瘤医院收治的3438例肺癌患者病例资料,回顾性分析其中70例合并肺癌MPM患者的临床病理特征。结果:同时多原发肿瘤(synchronous MPM,SMPM)16例,异时多原发肿瘤(metachronous MPM,MMPM)54例,男女比例为1∶1.06(男34例,女36例);入组病例次原发肿瘤发生的年龄为(61.37±11.22)岁;初原发肿瘤和次原发肿瘤发生平均时间间隔77.09月;肺癌先发组(lung cancer first,LCF)和其他器官肿瘤先发组(other cancer first,OCF)中肺癌病理类型均以肺腺癌最为多见,共42例(60.00%);肺癌分期为Ⅳ期患者共38例(54.29%);62.86%(44/70)患者伴有肺门或纵隔淋巴结转移;吸烟患者更容易出现SMPM。男性OCF组的初原发肿瘤中胃癌比例最高(31.82%,7/22),而原发性乳腺癌在女性中OCF组比例最高(32.26%,10/31)。结论:无病生存期超过5年的肿瘤患者应长期随访监测多原发肿瘤的发生;初原发乳腺癌、宫颈癌、胃癌患者应加强次原发肺癌的筛查,初原发肺癌患者应加强双原发肺癌及次原发胃癌、食管癌的筛查,以尽早发现MPM的发生,规范治疗,争取治愈机会。