Department of Medical Oncology, Institut Curie, 75005 Paris, France.
Department of Drug Development and Innovation (D3i), Institut Curie, 75005 Paris, France.
Int J Mol Sci. 2023 Jul 18;24(14):11570. doi: 10.3390/ijms241411570.
Somatic/germline mutations (m)/(likely) pathogenic variants (PV) (/) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic , combined tumor-based () and mutation testing () may improve the quality of results in somatic identification and interpretation of the 'second hit' event, i.e., loss of heterozygosity (LOH). A total of 237 patients with HGSOC underwent testing. The ratio of allelic fractions (AFs) for was calculated to estimate the proportion of cells carrying and to infer LOH. Among the 142/237 results, 16.2% demonstrated a pathogenic/deleterious variant (DEL) . Among the 195 contributive tumor samples, 43 DEL of (22.1%) were identified (23 and 20 with LOH identified in 37/41 conclusive samples. The median AF of was 0.52 (0.01-0.93), confirming huge variability in tumor cellularity. Initially, three samples were considered as wild type with <10% cellularity. However, additional testing detected a very low AF (<0.05) in both and , thus reidentifying them as . Combined testing is rapid, sensitive, and identifies somatic and germline AF is essential for interpreting in low-cellularity samples and provides indirect evidence for LOH as the 'second hit' of -related tumorigenesis.
体细胞/种系突变 (m)/(可能)致病性变异 (PV) (/仍然是 PARP 抑制剂疗效的最佳预测生物标志物。由于 >95%的高级别浆液性卵巢癌 (HGSOC) 具有体细胞，联合基于肿瘤的 () 和 突变测试 () 可能会提高体细胞识别的结果质量，并解释“第二次打击”事件，即杂合性丢失 (LOH)。共有 237 名 HGSOC 患者接受了 测试。计算等位基因分数 (AF) 的比例 以估计携带 的细胞比例，并推断 LOH。在 142/237 个 结果中，16.2%显示致病性/有害变异 (DEL) 。在 195 个有贡献的肿瘤样本中，鉴定出 43 个 (22.1%)的 DEL () (37/41 个结论性样本中有 23 个和 20 个 LOH)。 的中位 AF 为 0.52(0.01-0.93)，证实肿瘤细胞异质性很大。最初，三个样本被认为是细胞<10%的野生型。然而，额外的测试在 和 中检测到非常低的 AF(<0.05)，因此重新将它们鉴定为 。联合 测试快速、敏感，并识别体细胞和种系 。在低细胞量样本中解释 至关重要，并提供间接证据表明 LOH 是 -相关肿瘤发生的“第二次打击”。
