Molecular evidence of anaplastic transformation in coexisting well-differentiated and anaplastic carcinomas of the thyroid.
Anaplastic thyroid cancer is a rare but nearly universally fatal tumor. Epidemiologic data suggest that many anaplastic thyroid carcinomas arise from transformation of preexisting or coexisting well-differentiated thyroid carcinomas. At the molecular level, the mutations responsible for the anaplastic transformation are incompletely understood, although the mutational events are thought to involve tumor suppressor genes. To examine transformation from a well-differentiated thyroid carcinoma to anaplastic carcinoma, we studied coexisting well-differentiated (Hürthle cell and papillary carcinoma) and anaplastic tumors with a molecular genotyping panel of tumor suppressor genes associated with thyroid neoplasia. The patterns of allelic loss in our results showed that the majority of cases have a core of conserved mutations in the two morphologically distinct areas and substantial increases in mutation rates in the anaplastic components.
Hunt
Jennifer L
JL
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. huntj1@msx.upmc.edu
Tometsko
Michael
M
LiVolsi
Virginia A
VA
Swalsky
Patricia
P
Finkelstein
Sydney D
SD
Barnes
E Leon
EL
D018249:Adenoma, Oxyphilic / Q000235:genetics / Q000473:pathology; D000368:Aged; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers