VARIABILITY OF HA-RAS (CODON 12) PROTOONCOGENE MUTATIONS IN DIVERSE THYROID CANCERS

Structural alterations to proto-oncogene sequences may be involved in the pathogenesis of human thyroid neoplasms. We studied 128 thyroid tu mours (35 benign and 93 malignant) for las gene point mutations in thr ee different codons (12, 13 and 61) using a restriction fragment lengt h polymorphism technique and direct sequencing of double-stranded DMA on polymerase chain-reaction-amplified tumour DNA. We found a high fre quency of ras mutation for the Ha-ras codon 12 in follicular adenomas (7 of 35), particularly in atypical adenomas (5 of 17), in follicular carcinomas (6 of 19), with a high percentage for Hurthle cell carcinom as (6 of 11), and in papillary carcinomas (4 of 66), Point mutations f or other ras genes in different codons studied were weak to absent. No mutation was found in undifferentiated carcinomas (n = 8). The predom inant amino acid substitution both in the adenomas and in the differen tiated rumours was glycine to valine (GGC to GTC) at position 12 of th e Ha-ras gene. Our results obtained on a large series confirm the freq uent occurrence of Ha-ras codon 12 gene mutations both in adenomas and in carcinomas. The frequency of ras mutations is linked to the geogra phical origin of the population studied, and varies (0-85%) from one c ancer type to another according to published data. Therefore, these mu tations are merely an expression of cellular transformation.