Thyroid  1996 Oct;6(5):409-16 

Prevalence of activating ras mutations in morphologically characterized thyroid
nodules.

Ezzat S, Zheng L, Kolenda J, Safarian A, Freeman JL, Asa SL.

Department of Medicine, Wellesley Hospital, Toronto, Ontario, Canada.

Ras proteins are signal-transducing proteins that share common properties with
membrane-anchored G proteins. Mutations at codon 12/13 or codon 61 alter
GTP-binding or GTPase activity, respectively. Such activating mutations are
present in nearly 30-50% of various malignancies including colon, breast, and
lung carcinomas. There are conflicting data regarding the prevalence of ras
mutations in the thyroid and their possible pathogenetic role in the different
tumor types. To address this question, we examined 45 morphologically
characterized thyroid carcinomas, adenomas, and hyperplastic nodules using a
highly sensitive single-stranded conformation polymorphism (SSCP) approach
combined with DNA-sequencing. DNA from cell lines with known mutations served as
controls. A G to A H13 codon substitution replacing an Asp for a Gly residue was
detected in 1 papillary carcinoma. Although no H12 or H61 codon substitutions
were identified, 2 discrete alterations were identified in codons H17 and 22. No
N12/13 codon substitutions were identified. N61 codon substitutions of A to G
resulting in a Gly to Arg substitution were detected in 2 papillary carcinomas;
the same mutation was also found in one follicular adenoma. Interestingly,
K12/13 and K61 ras mutations were not present in any of the tumors examined.
These data establish a low prevalence of mutations in all ras gene family
members in human thyroid neoplasms. This difference from neoplasms of other
organs may explain the relatively indolent biologic behavior of many thyroid
tumors and supports an alternate early genetic mutation that is more
characteristic of these neoplasms.

PMID: 8936664 [PubMed - indexed for MEDLINE]