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Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas

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Abstract

Recent molecular studies have provided new insights into thyroid carcinogenesis. In thyroid papillary carcinomas at least three initiating events may occur, which are point mutations in the BRAF and RAS genes and RET/PTC rearrangements. Tumors harboring mutant BRAF and RAS are prone to progression to poorly differentiated and anaplastic carcinoma, but most likely require additional mutations to trigger this process. In thyroid follicular carcinomas, two known initiating events are RAS mutations and PAX8-PPARγ rearrangements, and RAS predisposes to dedifferentiation of follicular carcinomas. p53 and β-catenin mutations, found with increasing incidence in poorly differentiated and anaplastic carcinomas but not in well-differentiated tumors, may serve as a direct molecular trigger of tumor dedifferentiation. Additional evidence for progression from a preexisting well-differentiated carcinoma to poorly differentiated and anaplastic carcinoma comes from the studies of loss of heterozygosity and comparative genomic hybridization. Molecular studies, although limited by the lack of uniform histologic criteria for poorly differentiated carcinomas, revealed no genetic mutations or chromosomal abnormalities that are unique for poorly differentiated carcinoma and not present in well-differentiated or anaplastic carcinomas. This suggests that poorly differentiated carcinoma, as a group, represents a distinct step in the evolution from well-differentiated to anaplastic thyroid carcinoma, rather than an entirely separate type of thyroid malignancy.

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  1. Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH

    Yuri E. Nikiforov MD, PhD

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Correspondence to Yuri E. Nikiforov MD, PhD.

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Nikiforov, Y.E. Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas. Endocr Pathol 15, 319–327 (2004). https://doi.org/10.1385/EP:15:4:319

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