Increasing genome instability in adrenocortical carcinoma progression with involvement of chromosomes 3, 9 and X at the adenoma stage

Abstract

SummaryThe investigation of chromosomal aberrations in adrenocortical tumours has been limited by the difficulties of applying classical cytogenetics to tumours with low levels of proliferation. We have therefore applied the technique of interphase cytogenetics to paraffin-embedded archival specimens of 14 adrenocortical adenomas and 13 carcinomas. Hybridizations were performed using centromere-specific probes to chromosomes 3, 4, 9, 17, 18 and X, which have been shown to be altered in other types of tumours. Chromosomal imbalance was defined on the basis of changes in both chromosome index (CI) and signal distribution (SD). Where only one of these was altered, this was classified as a tendency to gain or loss. On the basis of the analysis of optimal hybridizations, carcinomas showed gains in all chromosomes studied, five of nine showing gains in multiple chromosomes. Gains were most common in chromosomes 3, 9 and, in particular X, eight of 11 showing gain, and one a tendency to gain. Chromosomal gain was seen less commonly in adenomas, but again chromosomes 3, 9 and X were involved. Losses were infrequent, only one carcinoma showing loss of chromosome 18, and adenomas showing a tendency to loss of chromosomes 4 (two cases), 17 (one case) and 18 (two cases). Our data suggest that changes in chromosomes 3, 9 and X are early events in adrenocortical tumorigenesis, and that there is increasing chromosomal instability with tumour progression.

Chromosomal aberrations in sporadic pituitary tumors

“…It also has to be taken into consideration that gain of chromosome X may represent an initial event in this neoplasm. Interestingly, FISH analysis on benign adrenocortical adenomas have also revealed a gain of the X chromosome in 72% of cases studied, 34 and further studies are required to elucidate the role of the X chromosome in the etiology of endocrine adenomas.…”

Comparative genomic hybridization analysis of thymic neuroendocrine tumors

“…Karyotyping or fluorescent in situ hybridization would be helpful to validate this speculation. Gain of the entire or partial copy of X chromosome have been found at high frequency in endocrine tumors such as pituitary adenoma 29 and adrenocortical adenoma, 30 as well as several solid and hematopoietic malignancies. [31][32][33] There is growing evidence that a few Xlinked genes are involved in the development of neoplasia.…”

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).…”