Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple endocrine neoplasia type 1 using whole-exome sequencing

BMC Medical Genetics

Case Report

Hyung Jin Choi¹  Ji Hoon Kim²  Bo-Young Kim³  Hae-Mi Woo³  Mi-Hyun Park³  Hye-Yeong Jo³  Soo Kyung Koo³ 

[1] Department of Anatomy, Department of Biomedical Science, Neuroscience Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, South Korea;Department of Surgery, Eulji University Hospital, Daejeon, South Korea;Division of Intractable Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeing2-ro, 28159, Cheongju-si, Chungcheongbuk-do, South Korea;

关键词: Multiple endocrine neoplasia type 1;    Genetic analysis;    Somatic mutation;    Whole-exome sequencing;    Clinical genomics;    Case report;   

DOI  :  10.1186/s12881-017-0465-9

 received in 2016-12-28, accepted in 2017-09-11,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMultiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant hereditary disorder characterized by the presence of endocrine tumors affecting the parathyroid, pancreas, and pituitary. A heterozygous germline inactivating mutation in the MEN1 gene (first hit) may be followed by somatic loss of the remaining normal copy or somatic mutations in the MEN1 gene (second hit). Whole-exome sequencing has been successfully used to elucidate the mutations associated with the different types of tumors.Case presentationWe performed whole-exome sequencing (WES) on three parathyroid tumors, one pancreatic insulinoma, and a blood sample taken from the same patient with MEN1 to study tumor heterogeneity in MEN1 originating from different tumors. We identified a novel frame-shift deletion (c.1382_1383delAG, p.E461GfsX69) in the MEN1 gene using WES, which was confirmed by Sanger sequencing. WES and the SNP array revealed somatic LOH on chromosome 11 in parathyroid tumors (left upper, left lower, and right upper parathyroid). However, we did not detect a somatic MEN1 gene mutation or LOH in the pancreatic insulinoma. WES revealed two somatic functional variants outside the MEN1 gene in the pancreatic insulinoma.ConclusionsThis study revealed heterogeneity among tumors in the same patient with MEN1, suggesting that different tumor-specific tumorigenic mechanisms may contribute to the pathogenesis of MEN1 tumors. The present study supports the clinical applicability of the WES strategy to research on multiple tumor samples and blood.

【 授权许可】

CC BY   
© The Author(s). 2017