Absence of activating mutations in ras and gsp oncogenes in a cohort of nine patients with sporadic pediatric thyroid tumors

Background. Characterization oi the genetic background oi pediatric thyroid carcinomas could aid in distinguishing between differently staged tumors w ith respect to treatment and prognosis Two known genetic factors associated with thyroid carcinoma, the proto-oncogenes gsp and ras were investigated. Procedure. DNA was extracted from paraffin sections from both tumor and no rmal thyroid tissue of nine patients (ages 9-16 years). Oi these patients, Fight were diagnosed with papillary carcinoma and one with follicular adeno ma, The coding exons of gsp and tile three known ras genes (H, K,and N-ras) were screened for mutations using SSCP-analysis. Results. There were no mu tations I,resent in the ras and gsp proto-oncogenes hot spots, however, LOH oi H-TRS (chromosome location 11p15.5) was found ii? tumor tissue from one patient and a homozygous mutation in exon 12 of Ssp causing a Pro --> Ser conversion was present in the thyroid tumor tissue from another patient. Tw o silent polymorphisms were detected, H-ras exon1, 86T --> C and gsp exon 5 , 81T --> C. Conclusions. Our results indicate that the ras/gsp mutations f ound are I,rot,ably late events in the tumorigenesis representing general o ncogenic stress. In conclusion, ii seems that ras/gsp activation is not a f actor in the mechanism causing sporadic thyroid carcinoma in children. (C) 2001 Wiley-Liss, Inc.