Department of Obstetrics and Gynecology, Fukushima Medical University, Fukushima, 960-1295, Japan.
Translational Research Center, Fukushima Medical University, Fukushima, 960-1295, Japan.
J Ovarian Res. 2021 Oct 6;14(1):129. doi: 10.1186/s13048-021-00876-z.
Epithelial ovarian cancer (EOC) is a heterogeneous disease with diverse clinicopathological features and behaviors, and its heterogeneity may be concerned with the accumulation of multiple somatic oncogenic mutations. The major goals of this study are to systematically perform the comprehensive mutational profiling in EOC patients, and investigate the associations between somatic mutations and clinicopathological characteristics.
A total of 80 surgical specimens were obtained from EOC patients who had previously undergone primary debulking surgery, and genomic DNAs were extracted from fresh-frozen tissues. We investigated mutational status in hot spot regions of 50 cancer-related genes by targeted next-generation sequencing using an Ion AmpliSeq Cancer Hotspot Panel v2 Kit.
Validated mutations were detected in 66 of the 80 tumors (82.5%). The five most frequently mutated genes were TP53 (43.8%), PIK3CA (27.5%), KRAS (23.8%), PTEN (10%) and CTNNB1 (10%). PTEN and CTNNB1 mutations were associated with younger age. PIK3CA1, KRAS and CTNNB1 mutations were observed in early-stage, whereas TP53 mutations were more common in advanced stage. Significant associations were observed between TP53 mutation and serous carcinoma, and between KRAS mutation and mucinous carcinoma. Both PIK3CA mutation and CTNNB1 mutation were also significantly associated with endometrioid and clear cell carcinoma. The patients with PIK3CA and KRAS mutations were significantly associated with favorable progression free survival (PFS). In particular, PIK3CA mutations had more significant associations with favorable PFS than PIK3CA wild-type in the endometrioid subtype (P = 0.012). Patients with mutations only in TP53 were significantly associated with worse PFS.
EOCs were heterogeneous at the genomic level and harbored somatic oncogenic mutations. Our molecular profiling may have the potential for becoming a novel stratification within histological subtypes of EOC. Further studies are needed to define molecular classification for improved clinical outcomes and treatment of EOC patients in future.
卵巢上皮癌（EOC）是一种具有不同临床病理特征和行为的异质性疾病，其异质性可能与多种体细胞致癌突变的积累有关。本研究的主要目的是系统地对 EOC 患者进行全面的突变分析，并研究体细胞突变与临床病理特征之间的关系。
从先前接受过初次减瘤手术的 EOC 患者的 80 例手术标本中获取了基因组 DNA。我们使用 Ion AmpliSeq Cancer Hotspot Panel v2 试剂盒通过靶向下一代测序对 50 个癌症相关基因的热点区域进行了突变状态的检测。
在 80 个肿瘤中有 66 个（82.5%）检测到了有效的突变。最常突变的五个基因是 TP53（43.8%）、PIK3CA（27.5%）、KRAS（23.8%）、PTEN（10%）和 CTNNB1（10%）。PTEN 和 CTNNB1 突变与年轻的年龄有关。PIK3CA1、KRAS 和 CTNNB1 突变发生在早期，而 TP53 突变在晚期更常见。TP53 突变与浆液性癌有关，KRAS 突变与黏液性癌有关。PIK3CA 突变和 CTNNB1 突变也与子宫内膜样癌和透明细胞癌显著相关。PIK3CA 和 KRAS 突变的患者与无进展生存期（PFS）显著相关。特别是，在子宫内膜样癌亚型中，PIK3CA 突变与良好的 PFS 相关程度比 PIK3CA 野生型更高（P=0.012）。仅 TP53 突变的患者与更差的 PFS 显著相关。
EOC 在基因组水平上具有异质性，存在体细胞致癌突变。我们的分子谱分析可能具有成为 EOC 组织学亚型新分层的潜力。需要进一步的研究来确定分子分类，以提高未来 EOC 患者的临床结果和治疗效果。
