■基因组分析在晚期或转移性癌症患者中进行,为了指导癌症治疗,通常只对肿瘤进行测序,没有匹配的种系比较器。然而,因为在肿瘤谱分析中分析的许多基因与已知与遗传性癌症易感性综合征(HCPS)相关的基因重叠,仅肿瘤分析可以在不知情的情况下发现种系致病性(P)和可能的致病性变异(LPV).在这项研究中,我们通过仅肿瘤分析评估了BRCA1和BRCA2(BRCA1/2)中确定的P/LPV患者数量,然后确定这些患者的种系测试结果。
■进行了回顾性图表审查,以确定仅肿瘤基因组分析中具有BRCA1/2变异的患者,以及他们是否进行了种系测试。
■这项研究发现,在2923名36种肿瘤类型的患者中,他们只接受了肿瘤检测,554例患者有BRCA1/2变异(19.0%);554例患者中有119例(21.5%)有P/LPBRCA1/2变异,代表接受基因组分析的总人口的4.1%。119例BRCA1/2P/LPV患者中有73例(61.3%)在仅肿瘤测试中没有进行种系测试,34人(28.6%)在仅肿瘤测试之前已经进行了种系测试,12例(10.1%)在仅肿瘤检测后接受了种系检测.检测到28种系BRCA1/2P/LPV,在那些先前进行了种系测试的人中,有24人,在仅肿瘤检测后进行种系检测的12例患者中,有4例。
■仅肿瘤检测可能在BRCA1/2中鉴定P/LPV。需要努力改进后续种系测试以改进种系BRCA1/2改变的鉴定。
UNASSIGNED: Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in BRCA1 and BRCA2 (BRCA1/2) via tumor-only profiling, then determined the germline testing outcomes for those patients.
UNASSIGNED: A retrospective chart review was performed to identify patients with BRCA1/2 variants on tumor-only genomic profiling, and whether they had germline testing.
UNASSIGNED: This study found that of 2923 patients with 36 tumor types who underwent tumor-only testing, 554 had a variant in BRCA1/2 (19.0%); 119 of the 554 patients (21.5%) had a P/LP BRCA1/2 variant, representing 4.1% of the overall population who underwent genomic profiling. Seventy-three (61.3%) of 119 patients with BRCA1/2 P/LPV on tumor-only testing did not undergo germline testing, 34 (28.6%) had already had germline testing before tumor-only testing, and 12 (10.1%) underwent germline testing after tumor-only testing. Twenty-eight germline BRCA1/2 P/LPVs were detected, 24 in those who had prior germline testing, and 4 among the 12 patients who had germline testing after tumor-only testing.
UNASSIGNED: Tumor-only testing is likely to identify P/LPVs in BRCA1/2. Efforts to improve follow-up germline testing is needed to improve identification of germline BRCA1/2 alterations.