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Journal of Cancer Research and Clinical Oncology

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18-09-2021 | Gastric Cancer | Original Article – Clinical Oncology

CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer

Authors: Zhiwen Pan, Zhixuan Fu, Cong Luo, Yejiang Bao, Mingli Wang, Wenming Cao, Xiaohong Xu

Published in: Journal of Cancer Research and Clinical Oncology | Issue 8/2022

Abstract

Purpose

Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer (HDGC) and have been identified in multiple ethnicities. However, CDH1 germline mutations have seldom been documented in Chinese patients with HDGC, and their frequency remains unclear. Here, we aimed to examine the frequency of CDH1 germline mutations in Chinese patients with HDGC. In total, 285 patients who met the International Gastric Cancer Linkage Consortium 2015 testing criteria of HDGC for CDH1 germline mutations were recruited.

Methods

All 16 CDH1 exons, including neighboring intronic sequences, were amplified using polymerase chain reaction and screened using Sanger sequencing. Variants were analyzed using Mutation Surveyor V4.0, SIFT, and PolyPhen-2 software.

Results

Three nonsense and nine missense CDH1 germline mutations were identified in 21 of 285 index cases (7.4%). Two CDH1 germline mutations, N405Y (Asn405Tyr) and W409X (Trp409Ter), were identified as new variants. In addition, up to 28.6% of CDH1 mutations in the 21 indicated patients were identified as c.1775G>C (E551Q). The frequency of CDH1 mutations was 6.5% (7/108) in HDGC and 7.9% (14/177) in early onset diffuse gastric cancer (EODGC). The mutation detection rates of CDH1 in males and females were 6.7% (4/60) and 8.5% (10/117) in EODGC and 4.6% (3/65) and 9.3% (4/43) in HDGC, respectively.

Conclusion

These data reveal, for the first time, the type and frequency of CDH1 germline mutations in Chinese HDGC and demonstrate that germline CDH1 mutations are a noteworthy contributor to the high frequency of HDGC in Chinese.

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Title: CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer
Authors: Zhiwen Pan
Zhixuan Fu
Cong Luo
Yejiang Bao
Mingli Wang
Wenming Cao
Xiaohong Xu
Publication date: 18-09-2021
Publisher: Springer Berlin Heidelberg
Keywords: Gastric Cancer
Gastric Cancer
Published in: Journal of Cancer Research and Clinical Oncology / Issue 8/2022
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-021-03775-4

PD Dr. Carsten W. Israel

Developed by: Springer Medizin

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