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

• Published in: BMC medical genetics Vol. 18; no. 1; p. 106
• Main Authors: Kim, Bo-Young, Park, Mi-Hyun, Woo, Hae-Mi, Jo, Hye-Yeong, Kim, Ji Hoon, Choi, Hyung Jin, Koo, Soo Kyung
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.10.2017; BioMed Central; BMC
• Subjects: Adult; Bioinformatics; Case Report; Case reports; Chromosome 11; Clinical genomics; Exome - genetics; Exome sequencing; Fasting; Gene deletion; Gene mutation; Genetic analysis; Genetic aspects; Genetic Testing - methods; Genomes; Germ-Line Mutation; Hereditary diseases; High-Throughput Nucleotide Sequencing - methods; Humans; Insulinoma; Insulinoma - genetics; Male; Multiple endocrine neoplasia; Multiple endocrine neoplasia type 1; Multiple Endocrine Neoplasia Type 1 - genetics; Mutation; Neuroendocrine tumors; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - complications; Pancreatic Neoplasms - genetics; Parathyroid; Parathyroid Neoplasms - complications; Parathyroid Neoplasms - genetics; Pedigree; Pituitary; Point mutation; Proto-Oncogene Proteins - genetics; Single-nucleotide polymorphism; Somatic mutation; Tumors; Whole-exome sequencing; Somatic mutation; Multiple endocrine neoplasia type 1; Case report; Clinical genomics; Whole-exome sequencing; Genetic analysis
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-017-0465-9

Multiple 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. We 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. This 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.