Jones Derek H, Lin Douglas I
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Mol Clin Oncol. 2017 Aug;7(2):301-307. doi: 10.3892/mco.2017.1289. Epub 2017 Jun 8.
Identification of novel therapeutics in pelvic high-grade serous carcinoma (HGSC) has been hampered by a paucity of actionable point mutations in target genes. The aim of the present study was to investigate the extent of amplification of the therapeutically targetable pathway in pelvic HGSC, and to determine whether amplification is associated with worse prognosis. The Cancer Genome Atlas (TCGA) ovarian and endometrial cancer cohorts were retrospectively analyzed via online data-mining tools to test the association of , and genomic alterations with survival of pelvic HGSC patients. It was demonstrated that amplification of the pathway in the ovarian HGSC cohort (observed in 18% of the cases, 88/489) was significantly associated with worse overall and progression-free survival compared with non-amplified cases. In addition, amplification of , and also occurred in 9% (21/232) of overall endometrial cancer TCGA cases, which was associated with worse overall survival. In the endometrial cancer TCGA cohort, , and amplification occurred specifically in the serous carcinoma (25%, 13/53) and 'serous-like' copy number high endometrial carcinoma (33%, 20/60) subgroups, compared with the polymerase e (0%, 0/17), microsatellite instability high (0%, 0/65) or low copy number (1%, 1/90) subgroups. These findings support the hypothesis that amplification of the axis is frequent in pelvic HGSC of both ovarian and endometrial origin, and that this pathway is potentially targetable in a subset of HGSC patients.
盆腔高级别浆液性癌（HGSC）中新型治疗方法的识别一直受到靶基因中可操作点突变缺乏的阻碍。本研究的目的是调查盆腔HGSC中可治疗靶向通路的扩增程度，并确定扩增是否与较差的预后相关。通过在线数据挖掘工具对癌症基因组图谱（TCGA）卵巢癌和子宫内膜癌队列进行回顾性分析，以测试 、 和 基因组改变与盆腔HGSC患者生存的相关性。结果表明，卵巢HGSC队列中 通路的扩增（在18%的病例中观察到，88/489）与未扩增病例相比，与较差的总生存期和无进展生存期显著相关。此外， 、 和 的扩增也发生在总体子宫内膜癌TCGA病例的9%（21/232）中，这与较差的总生存期相关。在子宫内膜癌TCGA队列中， 、 和 的扩增特别发生在浆液性癌（25%，13/53）和“浆液样”拷贝数高的子宫内膜癌（33%，20/60）亚组中，与聚合酶e（0%，0/17）、微卫星不稳定性高（0%，0/65）或低拷贝数（1%，1/90）亚组相比。这些发现支持了这样的假设，即 轴的扩增在卵巢和子宫内膜起源的盆腔HGSC中很常见，并且该通路在一部分HGSC患者中可能是可靶向的。
