Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications

Distinction of adrenocortical carcinoma from benign adrenocortical lesions by standard criteria is often difficult. In order to search for additional diagnostic parameters, a series of 25 adrenocortical tumors, 8 adenomas, 14 primary carcinomas, I metastasis, and the 2 adrenocortical carcinoma cell lines SW 13 and NCI-H295 were analyzed by the approach of comparative genom ic hybridization (CGH). Except for the two smallest adenomas, all tumors sh owed chromosomal imbalances with a high incidence of chromosomal gains, mos t frequently involving chromosomes or chromosome arms 5, 7, 8, 9q, 11q, 12q , 14q, 16, 17q, 19, 20, and 22q. The only significant loss of material conc erned the distal part of 9p. Furthermore, 21 high-level amplifications were identified in 15 different regions of the genome. The consensus regions of recurrent gains and the focal high-level amplifications allowed identifica tion of a series of chromosomal subregions containing candidate proto-oncog enes of potential pathogenic function in adrenocortical tumors: 1p34.3-pter , 1q22-q25, 3p24-pter, 3q29, 7p11.2-p14, 9q34, 11q12-11q13, 12q13, 12q24.3, 13q34, 149q11.2-q12, 14q32, 16p, 17q24-q25, 19q13.3, 19q13.4, and 22q11.2- q12. A subset of the CGH data was independently confirmed by interphase cyt ogenetics, Interestingly, the adenomas larger than 4 cm contained gained ma terial of regions also overrepresented in carcinomas. In addition, several chromosomal gains, in particular the high-level amplifications, were exclus ive for the malignant status of the tumors. These data indicate that the la rger adrenal lesions need to be carefully considered in the diagnosis of ad renocortical tumors, and that genetic aberrations might provide useful mark ers for a better diagnostic differentiation, Genes Chromosomes Cancer 28:14 5-152 2000. (C) 2000 Wiley-Liss, Inc.