Gain of 1q and loss of 9q21.3-q32 are associated with a less favorable prognosis in papillary thyroid carcinoma

In order to approach the genetic mechanisms behind initiation and progressi on of papillary thyroid carcinoma (PTC) tumorigenesis, we characterized num erical chromosomal imbalances in a panel of 25 PTCs with varying histopatho logical and clinical features using comparative genomic hybridization (CGH) . The most frequently detected imbalance was gain of 9q33-qter, which was s een in close to 30% of the cases. The commonly occurring regions of loss we re assigned to 22q (12%) and 9q21.3-q32 (12%), while gains preferentially i nvolved the entire X chromosome (20%), 1q (16%), 17q (16%), and 22q (12%). The distribution of CGH alterations supports the idea of a progression of g enetic events in the development of PTC, where gain of 9q33-qter would repr esent a relatively early event that is followed by loss of 22q and gain of X, Iq, 17q, and 22q. When the detected CGH alterations were compared with t he clinical outcome and the histopathological features of the 25 PTC cases, several statistically significant correlations were revealed. The total nu mber of genetic alterations was higher in tumors from patients with aggress ive disease as compared to those without signs of aggressiveness. Gain of I q and loss of 9q21.3-q32 were exclusively seen in tumors from patients with aggressive disease, and the presence of distant metastases was associated with gain of Iq. A sex-dependent distribution was also evident for one of t he common alterations, with gain of X exclusively seen in male cases. Taken together, the findings identify several candidate locations for tumor supp ressor genes and oncogenes that are potentially involved in the establishme nt and progression of papillary thyroid carcinogenesis. (C) 2001 Wiley-Liss , Inc.