Mutational analysis of the ret proto-oncogene in 71 japanese patients with medullary thyroid carcinoma

ABSTRACT Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinomas (FMTC) are caused by germline mutations in the _RET_ proto-oncogene. To

investigate the spectrum of _RET_ mutations among Japanese patients, we screened the _RET_ gene in 71 patients with thyroid carcinomas. The panel included representatives of 44 families

carrying FMTC or MEN2, 22 sporadic medullary thyroid carcinomas (MTCs), and five MTCs without familial information. Mutations in nucleotide sequences encoding one of three specific cysteine

residues in the extracellular domain of the _RET_ protein were found in 33 of the 34 MEN2A patients and in five of the six FMTC patients examined. A mutation at codon 918, causing the

substitution of threonine for methionine in the tyrosine kinase domain of the protein, was found in germline DNAs of all four patients with MEN2B and in two of the 22 patients with sporadic

MTCs; codon 918 was mutated somatically in tumor DNAs from three other sporadic cases. Germline mutations of codon 768, GAG to GAC (Glu to Asp), were detected in one FMTC, in one patient

with sporadic MTC, and in one of the patients without familial information. Two somatic mutations, an Asp to Gly substitution at codon 631 and a Cys to Arg substitution at codon 634, had not

been reported previously. Of five germline mutations found among the 22 sporadic cases, four were confirmed as de novo mutations since in each case neither parent carried the mutation. As

nearly one-fourth of the patients with sporadic MTCs carried germline mutations and 50% of their children are expected to develop MTC and other endocrine tumors, these results indicated the

importance of careful clinical surveillance of family members of any patient with MTC. SIMILAR CONTENT BEING VIEWED BY OTHERS KINOME PROFILING REVEALS PATHOGENIC VARIANT SPECIFIC PROTEIN

SIGNALLING NETWORKS IN MEN2 CHILDREN WITH MEDULLARY THYROID CANCER Article Open access 02 May 2025 THE IMPORTANCE OF THE _RET_ GENE IN THYROID CANCER AND THERAPEUTIC IMPLICATIONS Article 18

February 2021 IGF2BP1 IS THE FIRST POSITIVE MARKER FOR ANAPLASTIC THYROID CARCINOMA DIAGNOSIS Article Open access 27 July 2020 ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Center for Molecular Biology and Cytogenetics, SRL Inc., 5-6-50 Shinmachi, Hino-shi, Tokyo, 191-0002 Japan Tel. +81-426-48-3783; Fax +81-426-48-4054 e-mail: [email protected], Japan

Syuya Shirahama & K. Ogura * First Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan Hiroshi Takami * Ito Hospital, Tokyo, Japan, Japan Kunihiko Ito * Tohsen

Clinic, Syouwa, Japan, Japan Tohichi Tohsen * Second Department of Surgery, Kagawa Medical University, Miki, Japan, Japan Akira Miyauchi * Laboratory of Molecular Medicine, Institute of

Medical Science, University of Tokyo, Tokyo, Japan, Japan Yusuke Nakamura Authors * Syuya Shirahama View author publications You can also search for this author inPubMed Google Scholar * K.

Ogura View author publications You can also search for this author inPubMed Google Scholar * Hiroshi Takami View author publications You can also search for this author inPubMed Google

Scholar * Kunihiko Ito View author publications You can also search for this author inPubMed Google Scholar * Tohichi Tohsen View author publications You can also search for this author

inPubMed Google Scholar * Akira Miyauchi View author publications You can also search for this author inPubMed Google Scholar * Yusuke Nakamura View author publications You can also search

for this author inPubMed Google Scholar ADDITIONAL INFORMATION Received: August 22, 1997 / Accepted: October 22, 1997 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Shirahama, S., Ogura, K., Takami, H. _et al._ Mutational analysis of the _RET_ proto-oncogene in 71 Japanese patients with medullary thyroid carcinoma. _J Hum Genet_ 43, 101–106

(1998). https://doi.org/10.1007/s100380050048 Download citation * Published: 01 June 1998 * Issue Date: June 1998 * DOI: https://doi.org/10.1007/s100380050048 SHARE THIS ARTICLE Anyone you

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Springer Nature SharedIt content-sharing initiative * Key words Multiple endocrine neoplasia type 2 (MEN2) * Familial medullary thyroid carcinoma (FMTC) * Sporadic medullary thyroid

carcinoma (MTC) * RET proto-oncogene