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Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type

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). T...

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Autores principales: Uchino, Shinya, Noguchi, Shiro, Yamashita, Hiroto, Sato, Mari, Adachi, Mitsuo, Yamashita, Hiroyuki, Watanabe, Shin, Ohshima, Akira, Mitsuyama, Shoshu, Iwashita, Toshihide, Takahashi, Masahide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926019/
https://www.ncbi.nlm.nih.gov/pubmed/10622534
http://dx.doi.org/10.1111/j.1349-7006.1999.tb00701.x
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author Uchino, Shinya
Noguchi, Shiro
Yamashita, Hiroto
Sato, Mari
Adachi, Mitsuo
Yamashita, Hiroyuki
Watanabe, Shin
Ohshima, Akira
Mitsuyama, Shoshu
Iwashita, Toshihide
Takahashi, Masahide
author_facet Uchino, Shinya
Noguchi, Shiro
Yamashita, Hiroto
Sato, Mari
Adachi, Mitsuo
Yamashita, Hiroyuki
Watanabe, Shin
Ohshima, Akira
Mitsuyama, Shoshu
Iwashita, Toshihide
Takahashi, Masahide
author_sort Uchino, Shinya
collection PubMed
description 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.
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spelling pubmed-59260192018-05-11 Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type Uchino, Shinya Noguchi, Shiro Yamashita, Hiroto Sato, Mari Adachi, Mitsuo Yamashita, Hiroyuki Watanabe, Shin Ohshima, Akira Mitsuyama, Shoshu Iwashita, Toshihide Takahashi, Masahide Jpn J Cancer Res Article 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. Blackwell Publishing Ltd 1999-11 /pmc/articles/PMC5926019/ /pubmed/10622534 http://dx.doi.org/10.1111/j.1349-7006.1999.tb00701.x Text en
spellingShingle Article
Uchino, Shinya
Noguchi, Shiro
Yamashita, Hiroto
Sato, Mari
Adachi, Mitsuo
Yamashita, Hiroyuki
Watanabe, Shin
Ohshima, Akira
Mitsuyama, Shoshu
Iwashita, Toshihide
Takahashi, Masahide
Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type
title Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type
title_full Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type
title_fullStr Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type
title_full_unstemmed Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type
title_short Somatic Mutations in RET Exons 12 and 15 in Sporadic Medullary Thyroid Carcinomas: Different Spectrum of Mutations in Sporadic Type from Hereditary Type
title_sort somatic mutations in ret exons 12 and 15 in sporadic medullary thyroid carcinomas: different spectrum of mutations in sporadic type from hereditary type
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926019/
https://www.ncbi.nlm.nih.gov/pubmed/10622534
http://dx.doi.org/10.1111/j.1349-7006.1999.tb00701.x
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