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Association of recurrent APOBEC3B alterations with the prognosis of gastric-type cervical adenocarcinoma.

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机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China [3]Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China [4]Department ofThyroid and Parathyroid Surgery, Laboratory of thyroid and parathyroid disease, Frontiers Science Center for Disease- related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China [5]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [6]Department of Gastroenterology, The Afiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China [7]Sichuan Center for Translational Medicine of Traditional Chinese Medicine, Institute of Translational Pharmacology, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China [8]Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha, China [9]Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value.We performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis. The prognostic value of the genomic alterations was evaluated in a total of 58 GCA patients.Mutations were commonly observed in reported GCA-related driver genes, including TP53 (32%), CDKN2A (20%), SKT11 (20%), BRCA2 (12%), SMAD4 (12%), and ERBB2 (12%). Recurrent novel trunk mutations were also observed in PBRM1 (12%), FRMPD4 (12%), and NOP2 (8%) with high variant allele frequency. Moreover, enrichment of the APOBEC signature was attributed to frequent gain of somatic copy number alteration (SCNA) of APOBEC3B (20%), which perfectly matched the nuclear-positive staining of APOBEC3B through immunohistochemistry. In contrast, APOBEC3B alteration was absent in patients with conventional type of ECA (N = 52). Notably, positive APOBEC3B was consistently enriched in patients with favorable prognosis in both the discovery cohort and an additional 33 GCA patients, thus indicating a significant association with lower relapse risk of GCA independent of cancer stage (P = 0.02).Our results can aid understanding of the molecular basis of GCA in the Chinese population by providing genomic profiles and highlighting the potential prognostic value of APOBEC3B for GCA through routine clinical IHC.Copyright © 2022. Published by Elsevier Inc.

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出版当年[2022]版:
大类 | 2 区 医学
小类 | 1 区 妇产科学 2 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 1 区 妇产科学 2 区 肿瘤学
第一作者:
第一作者机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2]Department of Pathology, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China
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通讯机构: [1]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [5]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China [9]Department of Laboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China [*1]Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No.17, Section 3, South Renmin Road, Chengdu 610041, China. [*2]Department ofLaboratory Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, 610041, Sichuan, China. [*3]Institute ofranlational Phamacology, Sichuan Academy of Chinese Medicine Sciences, No.51, Setion 4, South Renmin Road, Chengdu 610041,
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