Genomic landscape of endometrial carcinomas of no specific molecular profile Journal Article
| Authors: | Momeni-Boroujeni, A.; Nguyen, B.; Vanderbilt, C. M.; Ladanyi, M.; Abu-Rustum, N. R.; Aghajanian, C.; Ellenson, L. H.; Weigelt, B.; Soslow, R. A. |
| Article Title: | Genomic landscape of endometrial carcinomas of no specific molecular profile |
| Abstract: | 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. © 2022, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
| Keywords: | mutation; endometrioid carcinoma; endometrial neoplasms; pathology; genomics; endometrium tumor; carcinoma, endometrioid; humans; prognosis; human; female |
| Journal Title: | Modern Pathology |
| Volume: | 35 |
| Issue: | 9 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2022-09-01 |
| Start Page: | 1269 |
| End Page: | 1278 |
| Language: | English |
| DOI: | 10.1038/s41379-022-01066-y |
| PUBMED: | 35365770 |
| PROVIDER: | scopus |
| PMCID: | PMC9427676 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |
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888Abu-Rustum -
1328Ladanyi -
793Soslow -
609Aghajanian -
633Weigelt -
136Vanderbilt -
31Nguyen -
109Ellenson
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