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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Data availability statement
All datasets analyzed for this study are included in the manuscript/supplementary files.
Code availability
Not applicable.
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Acknowledgements
We would like to thank Editage (www.editage.com) for English language editing.
Funding
This study was supported by the Medical and Health Science Project of Zhejiang Province (2015KYA033, 2016139538, 2017KY021). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Conceptualization: ZP, CL, and XX. Data curation: MW, WC, ZP, and ZF. Writing – original draft: ZP and XX. Supervision and writing – review & editing: ZP, ZF, CL, YB, MW, WC, and XX.
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The protocol of the study was approved by the Ethics Committee of the Zhejiang Cancer Hospital (Approval No. IRB-2017-47). All subjects provided written informed consent in accordance with the Declaration of Helsinki.
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Pan, Z., Fu, Z., Luo, C. et al. CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer. J Cancer Res Clin Oncol 148, 2145–2151 (2022). https://doi.org/10.1007/s00432-021-03775-4
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DOI: https://doi.org/10.1007/s00432-021-03775-4