Open AccessSomatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type
Author(s) -
Uchino Shinya,
Noguchi Shiro,
Yamashita Hiroto,
Sato Mari,
Adachi Mitsuo,
Yamashita Hiroyuki,
Watanabe Shin,
Ohshima Akira,
Mitsuyama Shoshu,
Iwashita Toshihide,
Takahashi Masahide
Publication year - 1999
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.1349-7006.1999.tb00701.x
Subject(s) - exon , point mutation , germline mutation , multiple endocrine neoplasia type 2 , proto oncogene proteins c ret , mutation , genetics , biology , thyroid carcinoma , multiple endocrine neoplasia , ret proto oncogene , somatic cell , medullary carcinoma , cancer research , gene , microbiology and biotechnology , thyroid , receptor , neurotrophic factors , glial cell line derived neurotrophic factor
Germline mutations in the RET proto‐oncogene are responsible for multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Point mutations or in‐frame deletions of exons 10, 11, 13, 14 and 16 are associated with sporadic medullary thyroid carcinoma (MTC). To understand further the role of the RET gene in sporadic MTC, we examined mutations in exons 12 and 15 of RET in patients with sporadic MTC. DNAs were extracted from 39 formalin‐fixed tumor tissues and corresponding normal thyroid tissues or peripheral blood leukocytes. DNA sequencing was used to identify mutations in exons 12 and 15 of RET. In this study, one novel somatic mutation was found in exon 12 and five novel mutations or deletions were found in exon 15. Of the patients with mutations, one had an in‐frame 12‐bp deletion (nt. 2625‐2636), one had point mutations in both codons 884 and 908, and the remaining three had point mutations in codons 748, 876 and 901, respectively. Together with our previous identification of somatic mutations in exons 10, 11, 13, 14 and 16, somatic alterations were found in 10 out of 39 (25.6%) sporadic MTCs. There was no association of RET gene mutations with tumor recurrence or prognosis. These results suggest that mutations occur frequently in the RET coding region in addition to the previously reported mutation hot spots, and there is a different spectrum of mutations between sporadic and hereditary MTC.