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

Abstract

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, 1 metastasis, and the 2 adrenocortical carcinoma cell lines SW13 and NCI‐H295 were analyzed by the approach of comparative genomic hybridization (CGH). Except for the two smallest adenomas, all tumors showed chromosomal imbalances with a high incidence of chromosomal gains, most 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 concerned 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 identification of a series of chromosomal subregions containing candidate proto‐oncogenes 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, 14q11.2–q12, 14q32, 16p, 17q24–q25, 19p13.3, 19q13.4, and 22q11.2–q12. A subset of the CGH data was independently confirmed by interphase cytogenetics. Interestingly, the adenomas larger than 4 cm contained gained material of regions also overrepresented in carcinomas. In addition, several chromosomal gains, in particular the high‐level amplifications, were exclusive for the malignant status of the tumors. These data indicate that the larger adrenal lesions need to be carefully considered in the diagnosis of adrenocortical tumors, and that genetic aberrations might provide useful markers for a better diagnostic differentiation. Genes Chromosomes Cancer 28:145–152, 2000. © 2000 Wiley‐Liss, Inc.

Adrenocortical carcinoma survival rates correlated to genomic copy number variants

“…Additional studies have identified loss of heterozygosity at 17p13 and 11p15 along with increased expression of insulin-like growth factor 2 as molecular events associated with progression toward a malignant phenotype (15). As reported by Dohna et al, gains and high-level amplifications in chromosomes 7, 14, and 19 were seen only in ACC and not in benign adrenocortical neoplasms, suggesting that these events may be late genetic perturbations in tumorigenesis (16). Deletions have also been found within chromosomes 1p and 17p implicating potential losses of tumor suppressor genes in these regions, marking the progression of benign adrenal adenoma to ACC (17).…”

Mechanisms underlying losses of heterozygosity in human colorectal cancers

“…Such defects may include those affecting cell cycle checkpoints and centrosome number (46). These defects would explain the aneuploidy present in benign tumors (45,47,48) and would account for those cases in our study involving whole chromosome loss. The second proposed defect, however, cannot be accounted for by such well studied mechanisms.…”

Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

“…Characteristics of these gene sets are presented in Table 3. Cytogenetic (CGH and FISH) data on adrenocortical tumours were acquired from 10 publications found by literature search (Kjellman et al, 1996;Figueiredo et al, 1999Figueiredo et al, , 2005Russell et al, 1999;Zhao et al, 1999Zhao et al, , 2002Dohna et al, 2000;Sidhu et al, 2002;Bertherat et al, 2003;Stephan et al, 2008). These included 87 ACA and 124 ACC samples (Supplementary Table 3).…”