Open AccessGerm Line Mutations of the ret Proto‐oncogene in Japanese Patients with Multiple Endocrine Neoplasia Type 2A and Type 2B
Author(s) -
Maruyama Shoichi,
Iwashita Toshihide,
Imai Tsuneo,
Funahashi Hiroomi,
Ceccherini Isabella,
Luo Yin,
Romeo Giovanni,
Matsuo Seiichi,
Matsuyama Mutsushi,
Takahashi Masahide
Publication year - 1994
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1994.tb02962.x
Subject(s) - ret proto oncogene , missense mutation , multiple endocrine neoplasia type 2 , proto oncogene proteins c ret , multiple endocrine neoplasia , point mutation , mutation , biology , oncogene , allele , medullary thyroid cancer , cancer research , genetics , microbiology and biotechnology , thyroid , thyroid carcinoma , cancer , gene , germline mutation , receptor , cell cycle , neurotrophic factors , glial cell line derived neurotrophic factor
We investigated mutations of the ret proto‐oncogene in Japanese patients with multiple endocrine neoplasia (MEN) type 2A and type 2B. DNAs from pheochromocytomas and/or medullary thyroid carcinomas (MTCs) of five MEN 2A and three MEN 2B patients were amplified by a polymerase chain reaction (PCR) and analyzed. Tumors of four MEN 2A patients had missense mutations in Cys 634 in the extracellular domain of the ret proto‐oncogene. The same mutations were detected in normal tissues of the patients, indicating that the mutations had arisen in the germ line. Using a reverse transcriptase(RT)‐PCR, both normal and mutant transcripts of the ret proto‐oncogene were detected in a tumor of one patient with MEN 2A mutation. In addition, three MEN 2B patients examined had the same point mutation (ATGÂG) at codon 918 in the tyrosine kinase domain of the ret proto‐oncogene. Since all mutations identified in this study generated new restriction enzyme sites or eliminated a restriction site, the mutant alleles of affected family members could be readily detected without sequencing.