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Prevalence of Ras mutations in thyroid neoplasia
Author(s) -
Esapa Christopher T.,
Johnson Sarah J.,
KendallTaylor Pat,
Lennard Tom W. J.,
Harris Philip E.
Publication year - 1999
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.1999.00704.x
Subject(s) - adenoma , thyroid carcinoma , thyroid , mutation , follicular phase , medicine , biology , anaplastic carcinoma , pathogenesis , cancer research , pathology , endocrinology , gene , genetics
OBJECTIVE Mutations at codons 12, 13 or 61 of ras which result in constitutive activation occur frequently in human malignancies. There have been varied reports on their prevalence and hence their likely significance in the pathogenesis of primary thyroid neoplasia. To address this, we have examined a large series of benign and malignant thyroid tumours for ras mutations. DESIGN Genomic DNA was analysed for the presence of mutations at codons 12, 13 and 61 of H‐ ras , K‐ ras and N‐ ras by allele‐specific oligonucleotide hybridization. Direct DNA sequencing was used to confirm the mutations. PATIENTS A total of 90 samples with benign (66) and malignant (24) thyroid disease were investigated. RESULTS A total of 14/90 (15.5%) samples had a ras mutation. All mutations were at codon 61 of either N‐ ras or K‐ ras . The positive cases were 1/25 (4%) nodular goitre, 7/38 (18%) follicular adenoma, 4/9 (44%) follicular carcinoma, 1/1 anaplastic carcinoma, 1/1 follicular variant of papillary carcinoma, and 1 metastatic follicular carcinoma in which the primary tumour had the same mutation. CONCLUSIONS Our data demonstrate a relatively low overall prevalence of ras mutations in thyroid neoplasia, with a predominance in follicular neoplasms. Their presence in follicular adenomas suggests that they may have an early aetiological role in the development of thyroid neoplasia.