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Genetic characteristics of gastric-type mucinous carcinoma of the uterine cervix
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Genetic characteristics of gastric-type mucinous carcinoma of the uterine cervix
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Journal Article
Genetic characteristics of gastric-type mucinous carcinoma of the uterine cervix
2021
Overview
Gastric-type mucinous carcinoma (GAS) is a recently established variant of endocervical mucinous adenocarcinoma that is characterized as being unrelated to HPV and having aggressive behavior and chemoresistance. GAS has a distinct morphology resembling nonneoplastic gastric glands or pancreaticobiliary adenocarcinoma, and their possible genetic similarity has been posed. In this study, next-generation sequencing was performed in 21 GAS cases using a customized panel including 94 cancer-associated genes. A total of 54 nonsynonymous somatic mutations were detected with an average mutation rate of 2.6 per lesion (range: 0–9). The most frequently mutated gene was TP53 (11/21, 52.4%), followed by STK11, HLA-B, PTPRS (4/21, 19.0%), FGFR4 (3/21, 14.3%), GNAS, BRCA2, ELF3, ERBB3, KMT2D, SLX4 (2/21, 9.5%), CDH1, EPCAM, KRAS, MLH1, RNF43, SNAI1, TWIST1, ZEB1, ZEB2, and so on (1/21, 4.8%). The mutated genes were mostly involved in signal transduction, DNA damage repair, and epithelial–mesenchymal transition (EMT). Correlation of TP53 mutation and p53 protein expression demonstrated that 31.3% with abnormal p53 expression harbored wild-type TP53. Compared to genetic features of gastric and pancreaticobiliary adenocarcinoma, TP53 mutations were frequent in both GAS and gastrointestinal adenocarcinoma. While KMT2D, ERBB3, and RNF43 mutations were shared between GAS and gastric adenocarcinoma, highly mutated genes in pancreatic ductal adenocarcinoma such as KRAS, SMAD4, and CDKN2A were rarely mutated in GAS. Of frequently mutated genes in cholangiocarcinoma, BAP1 and HLA-B were identified in GAS. Frequent EMT-related gene mutations suggested a possible role of EMT-related pathways in tumor dissemination and chemoresistance of GAS. In addition, GAS shared some genetic features with gastrointestinal adenocarcinoma. These findings provide a clue in understanding the biological basis of GAS.
Publisher
Elsevier Inc,Nature Publishing Group US,Elsevier Limited
Subject
/ 45/22
/ 82/51
/ Adult
/ Aged
/ Biomarkers, Tumor - analysis
/ Biomarkers, Tumor - genetics
/ Cervix
/ Female
/ Fibroblast growth factor receptor 4
/ Genes
/ Genetic Predisposition to Disease
/ High-Throughput Nucleotide Sequencing
/ Histocompatibility antigen HLA
/ Humans
/ Medicine
/ Mutation
/ Neoplasms, Cystic, Mucinous, and Serous - chemistry
/ Neoplasms, Cystic, Mucinous, and Serous - genetics
/ Neoplasms, Cystic, Mucinous, and Serous - pathology
/ Pancreas
/ Uterine Cervical Neoplasms - chemistry
/ Uterine Cervical Neoplasms - genetics
/ Uterine Cervical Neoplasms - pathology
/ Uterus
