Simultaneous occurrence of PAX8-PPARg and RET-PTC3 rearrangements in a follicular variant of papillary thyroid carcinoma.
Specific genotype-phenotype correlations have been identified in conventional-type papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). In contrast, the genetic alterations underlying the pathogenesis of the follicular variant of PTC (FV-PTC), which shares some clinicopathologic and molecular features with both PTC and FTC, remain to be clarified. This entity shows a PAX8-PPARg fusion gene (associated with FTC), more frequently than BRAF or RET-PTC alterations (associated with PTC). Herein, we report, for the first time, an FV-PTC with the simultaneous occurrence of both RET-PTC and PAX8-PPARg alterations. Neoplastic cells were of the wild type for BRAF and H,K,N-RAS, had an apparently normal karyotype by conventional cytogenetics, and had a balanced genome by array comparative genomic hybridization analysis. In fact, submicroscopic chromosome rearrangements producing RET-PTC3 and PAX8-PPARg chimeric genes were found by interphase fluorescence in situ hybridization. We demonstrated that these 2 genetic alterations coexisted in the same tumor and were confined to 2 different clones. Our findings indicate that molecular heterogeneity, although an uncommon phenomenon, may occur in thyroid carcinoma and demonstrate the coexistence in a case of FV-PTC not only of the histologic but also of the molecular features of both PTC (RET-PTC) and FTC (PAX8-PPARg).
Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Italy.
Paola
P
Caria
Tinuccia
T
Dettori
Daniela Virginia
DV
Frau
Enrico
E
Di Oto
Luca
L
Morandi
Alfredo
A
Parmeggiani
Giovanni
G
Tallini
Roberta
R
Vanni
D018265:Carcinoma, Papillary, Follicular / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D056918:Nuclear Receptor Coactivators / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D013965:Thyroidectomy
D004273:DNA, Neoplasm; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015514:Oncogene Proteins, Fusion; C551995:PAX8-PPARgamma fusion protein, human