title: Genome-wide appraisal of thyroid cancer progression.
abstract: Several lines of evidence suggest that follicular cell-derived thyroid cancers represent a continuum of disease that progresses from the highly curable well-differentiated thyroid cancers to the universally fatal anaplastic cancers. However, the genetic mechanisms underlying thyroid cancer progression remain ill defined. We compared the molecular-cytogenetic profiles derived from comparative genomic hybridization (CGH) analysis of major histological variants of thyroid cancer to define genetic variables associated with progression. Overall, a sequential increase in chromosomal complexity was observed from well-differentiated papillary thyroid cancer to poorly differentiated and anaplastic carcinomas, both in terms of the presence of CGH detectable abnormalities (P = 0.003) and the median number of abnormalities per case (P < 0.001). The presence of multiple abnormalities common to all thyroid cancer variants, including gains of 5p15, 5q11-13, 19p, and 19q and loss of 8p, suggests that these tumors are derived from a common genetic pathway. Gains of 1p34-36, 6p21, 9q34, 17q25, and 20q and losses of 1p11-p31, 2q32-33, 4q11-13, 6q21, and 13q21-31 may represent secondary events in progression, as they were only detected in poorly differentiated and anaplastic carcinomas. Finally, recurrent gains at 3p13-14 and 11q13, and loss of 5q11-31 were unique to anaplastic carcinomas, suggesting they may be markers for anaplastic transformation. Our data suggests that the development of chromosomal instability underlies the progression to more aggressive phenotypes of thyroid cancer and sheds light on the possible genomic aberrations that may be selected for during this process.
authors.affiliation: Laboratory of Epithelial Cancer Biology, Head and Neck Service, New York, New York 10021, USA.
authors.forename: Volkert B
authors.initials: VB
authors.lastname: Wreesmann
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Ghossein
authors.forename: Snehal G
authors.initials: SG
authors.lastname: Patel
authors.forename: Charles P
authors.initials: CP
authors.lastname: Harris
authors.forename: Erik A
authors.initials: EA
authors.lastname: Schnaser
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shaha
authors.forename: R Michael
authors.initials: RM
authors.lastname: Tuttle
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: Pulivarthi H
authors.initials: PH
authors.lastname: Rao
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D015203:Reproducibility of Results; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*