Massively parallel sequencing analysis of 68 gastric-type cervical adenocarcinomas reveals mutations in cell cycle-related genes and potentially targetable mutations Journal Article
| Authors: | Selenica, P.; Alemar, B.; Matrai, C.; Talia, K. L.; Veras, E.; Hussein, Y.; Oliva, E.; Beets-Tan, R. G. H.; Mikami, Y.; McCluggage, W. G.; Kiyokawa, T.; Weigelt, B.; Park, K. J.; Murali, R. |
| Article Title: | Massively parallel sequencing analysis of 68 gastric-type cervical adenocarcinomas reveals mutations in cell cycle-related genes and potentially targetable mutations |
| Abstract: | Gastric-type cervical adenocarcinoma (GCA) is an aggressive type of endocervical adenocarcinoma characterized by mucinous morphology, gastric-type mucin, lack of association with human papillomavirus (HPV) and resistance to chemo/radiotherapy. We characterized the landscape of genetic alterations in a large cohort of GCAs, and compared it with that of usual-type HPV-associated endocervical adenocarcinomas (UEAs), pancreatic adenocarcinomas (PAs) and intestinal-type gastric adenocarcinomas (IGAs). GCAs (n = 68) were subjected to massively parallel sequencing targeting 410–468 cancer-related genes. Somatic mutations and copy number alterations (CNAs) were determined using validated bioinformatics methods. Mutational data for UEAs (n = 21), PAs (n = 178), and IGAs (n = 148) from The Cancer Genome Atlas (TCGA) were obtained from cBioPortal. GCAs most frequently harbored somatic mutations in TP53 (41%), CDKN2A (18%), KRAS (18%), and STK11 (10%). Potentially targetable mutations were identified in ERBB3 (10%), ERBB2 (8%), and BRAF (4%). GCAs displayed low levels of CNAs with no recurrent amplifications or homozygous deletions. In contrast to UEAs, GCAs harbored more frequent mutations affecting cell cycle-related genes including TP53 (41% vs 5%, p < 0.01) and CDKN2A (18% vs 0%, p = 0.01), and fewer PIK3CA mutations (7% vs 33%, p = 0.01). TP53 mutations were less prevalent in GCAs compared to PAs (41% vs 56%, p < 0.05) and IGAs (41% vs 57%, p < 0.05). GCAs showed a higher frequency of STK11 mutations than PAs (10% vs 2%, p < 0.05) and IGAs (10% vs 1%, p < 0.05). GCAs harbored more frequent mutations in ERBB2 and ERBB3 (9% vs 1%, and 10% vs 0.5%, both p < 0.01) compared to PAs, and in CDKN2A (18% vs 1%, p < 0.05) and KRAS (18% vs 6%, p < 0.05) compared to IGAs. GCAs harbor recurrent somatic mutations in cell cycle-related genes and in potentially targetable genes, including ERBB2/3. Mutations in genes such as STK11 may be used as supportive evidence to help distinguish GCAs from other adenocarcinomas with similar morphology in metastatic sites. © 2020, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
| Journal Title: | Modern Pathology |
| Volume: | 34 |
| Issue: | 6 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2021-06-01 |
| Start Page: | 1213 |
| End Page: | 1225 |
| Language: | English |
| DOI: | 10.1038/s41379-020-00726-1 |
| PUBMED: | 33318584 |
| PROVIDER: | scopus |
| PMCID: | PMC8154628 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 July 2021 -- Source: Scopus |
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