PTEN公司
子宫内膜癌
拷贝数分析
癌症研究
危险系数
生物
内科学
肿瘤科
医学
癌症
基因
拷贝数变化
遗传学
基因组
PI3K/AKT/mTOR通路
置信区间
细胞凋亡
作者
Amir Momeni Boroujeni,Bastien Nguyen,Chad Vanderbilt,Marc Ladanyi,Nadeem R. Abu‐Rustum,Carol Aghajanian,Lora H. Ellenson,Britta Weigelt,Robert A. Soslow
出处
期刊:Modern Pathology
[Springer Nature]
日期:2022-09-01
卷期号:35 (9): 1269-1278
被引量:43
标识
DOI:10.1038/s41379-022-01066-y
摘要
Endometrial carcinomas (ECs) classified by The Cancer Genome Atlas (TCGA) as copy number-low (also referred to as “no specific molecular profile” [NSMP]) have a prognosis intermediate between POLE-mutated and copy number-high ECs. NSMP-ECs are a heterogeneous group, however, comprising both relatively indolent and aggressive ECs. We identified a total of 472 NSMP-ECs among 1,239 ECs that underwent clinical sequencing of 410–468 cancer-related genes. Somatic mutation and copy number alteration data were subjected to unsupervised hierarchical clustering, which identified three genomic clusters. Random sampling with stratification was used to choose ~80 endometrioid ECs from each cluster, resulting in a study size of 240 endometrioid ECs as well as an additional 44 non-endometrioid NSMP-ECs. Cluster 1 (C1, n = 80) consisted primarily of NSMP-ECs with PTEN and PIK3R1 mutations, Cluster 2 (C2, n = 81) of tumors with PTEN and PIK3CA mutations and Cluster 3 (C3, n = 79) of NSMP-ECs with chromosome 1q high-level gain and lack of PTEN mutations. The majority (72.7%) of non-endometrioid NSMP-ECs mapped to C3. NSMP-ECs from C3 were more likely to be FIGO grade 3 (30%), estrogen receptor-negative/weak (54.5%) and FIGO stages III or IV. In multivariate analysis, molecular clusters were associated with worse overall survival outcomes with C3 tumors having the worst (hazard ratio: 4) and C1 tumors having the best outcome. In conclusion, NSMP-ECs are a heterogenous group of tumors and comprise both aggressive and clinically low-risk ECs that can be identified based on mutation and copy number data.
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