Convergence between germline and somatic mutations in pancreatic neuroendocrine tumors

in European Journal of Endocrinology
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  • 1 The Laboratory of Clinical Genetics, Medical Research Center
  • | 2 Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
  • | 3 State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
  • | 4 Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission of the People’s Republic of China, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
  • | 5 Department of Pathology, Peking Union Medical College Hospital, and Molecular Pathology Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

Correspondence should be addressed to A Tong or Y Zhao or W Wu; Email: tonganli@hotmail.com or zhao8028@263.net or doctorwuu@126.com

*(C Ling, X Hong and M Xu contributed equally to this work)

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Objectives

The pancreatic neuroendocrine tumors (PanNETs) are a group of clinically heterogeneous neoplasms. Although previous studies illustrated the somatic mutation pattern for PanNETs, the germline mutation pattern is still unclear. Here, we comprehensively screened the underlying germline mutations in a cohort of multiple endocrine neoplasia type 1 (MEN1)-related and sporadic PanNETs to reveal the characteristics of germline mutation in PanNET patients.

Methods

Patients diagnosed with PanNETs by biopsy or surgical pathology were enrolled in this study. Peripheral blood samples were used for genomic DNA purification and subsequent sequencing. The following sequencing techniques were used and compared for validation: (1) targeted gene capture with a customized panel; (2) whole exome sequencing data from previous study.

Results

A total of 184 PanNET patients were enrolled, including 20 MEN1-related and 164 sporadic cases. In this study, MEN1 mutation rate in MEN1-related PanNETs was 60% (12/20), of which 50% were novel mutation sites. For sporadic PanNETs, the overall germline mutation rate was very low. Besides the rare MEN1 mutation, previously unreported germline variant in DAXX was found in one non-functional PanNET.

Conclusions

This study revealed distinctive germline mutation rates between MEN1-related and sporadic PanNETs. The novel MEN1 mutations contribute to revealing the spectrum of MEN1 mutations in PanNETs. The newly discovered germline variant of DAXX in sporadic PanNET implies a tendency of convergence between germline and somatic mutation genes.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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