Absence of activating mutations in ras and gsp oncogenes in a cohort of nine patients with sporadic pediatric thyroid tumors.
BACKGROUND
Characterization of the genetic background of pediatric thyroid carcinomas could aid in distinguishing between differently staged tumors with respect to treatment and prognosis. Two known genetic factors associated with thyroid carcinoma, the proto-oncogenes gsp and ras were investigated.


METHODS
DNA was extracted from paraffin sections from both tumor and normal thyroid tissue of nine patients (ages 9-16 years). Of these patients, eight were diagnosed with papillary carcinoma and one with follicular adenoma. The coding exons of gsp and the three known ras genes (H, K, and N-ras) were screened for mutations using SSCP-analysis.


RESULTS
There were no mutations present in the ras and gsp proto-oncogenes hot spots, however, LOH of H-ras (chromosome location 11p15.5) was found in tumor tissue from one patient and a homozygous mutation in exon 12 of gsp causing a Pro-->Ser conversion was present in the thyroid tumor tissue from another patient. Two silent polymorphisms were detected, H-ras exon1, 86T-->C and gsp exon 5, 81T-->C.


CONCLUSIONS
Our results indicate that the ras/gsp mutations found are probably late events in the tumorigenesis representing general oncogenic stress. In conclusion, it seems that ras/gsp activation is not a factor in the mechanism causing sporadic thyroid carcinoma in children.
Pauws
E
E
Department of Pediatric Endocrinology G2-106, Academic Medical Center, University of Amsterdam, Emma Children's Hospital, AMC, Amsterdam, The Netherlands. e.pauws@amc.uva.nl
Tummers
R F
RF
Ris-Stalpers
C
C
de Vijlder
J J
JJ
Voûte
T
T
D000293:Adolescent; D002277:Carcinoma / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D013964:Thyroid Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D019205:GTP-Binding Protein alpha Subunits, Gs