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Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple endocrine neoplasia type 1 using whole-exome sequencing.
BMC Med Genet. 2017 10 02; 18(1):106.BM

Abstract

BACKGROUND

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.

CASE PRESENTATION

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.

CONCLUSIONS

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.

Authors+Show Affiliations

Division of Intractable Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.Division of Intractable Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.Division of Intractable Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.Division of Intractable Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 28159, South Korea.Department of Surgery, Eulji University Hospital, Daejeon, South Korea.Department of Anatomy, Department of Biomedical Science, Neuroscience Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, South Korea. hjchoi@snu.ac.kr.Division of Intractable Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeing2-ro, Cheongju-si, Chungcheongbuk-do, 28159, South Korea. skkoo@nih.go.kr.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28969599

Citation

Kim, Bo-Young, et al. "Genetic Analysis of Parathyroid and Pancreatic Tumors in a Patient With Multiple Endocrine Neoplasia Type 1 Using Whole-exome Sequencing." BMC Medical Genetics, vol. 18, no. 1, 2017, p. 106.
Kim BY, Park MH, Woo HM, et al. Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple endocrine neoplasia type 1 using whole-exome sequencing. BMC Med Genet. 2017;18(1):106.
Kim, B. Y., Park, M. H., Woo, H. M., Jo, H. Y., Kim, J. H., Choi, H. J., & Koo, S. K. (2017). Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple endocrine neoplasia type 1 using whole-exome sequencing. BMC Medical Genetics, 18(1), 106. https://doi.org/10.1186/s12881-017-0465-9
Kim BY, et al. Genetic Analysis of Parathyroid and Pancreatic Tumors in a Patient With Multiple Endocrine Neoplasia Type 1 Using Whole-exome Sequencing. BMC Med Genet. 2017 10 2;18(1):106. PubMed PMID: 28969599.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple endocrine neoplasia type 1 using whole-exome sequencing. AU - Kim,Bo-Young, AU - Park,Mi-Hyun, AU - Woo,Hae-Mi, AU - Jo,Hye-Yeong, AU - Kim,Ji Hoon, AU - Choi,Hyung Jin, AU - Koo,Soo Kyung, Y1 - 2017/10/02/ PY - 2016/12/28/received PY - 2017/09/11/accepted PY - 2017/10/4/entrez PY - 2017/10/4/pubmed PY - 2017/10/14/medline KW - Case report KW - Clinical genomics KW - Genetic analysis KW - Multiple endocrine neoplasia type 1 KW - Somatic mutation KW - Whole-exome sequencing SP - 106 EP - 106 JF - BMC medical genetics JO - BMC Med. Genet. VL - 18 IS - 1 N2 - BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/28969599/Genetic_analysis_of_parathyroid_and_pancreatic_tumors_in_a_patient_with_multiple_endocrine_neoplasia_type_1_using_whole_exome_sequencing_ L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-017-0465-9 DB - PRIME DP - Unbound Medicine ER -