Adrenocortical carcinoma survival rates correlated to genomic copy number variants

Abstract

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02% and 0.2% of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in 40% to 70% of patients at the time of diagnosis. Standard chemotherapy with mitotane is often ineffective with intolerable side effects. The modern molecular technology of comparative genomic hybridization allows the examination of DNA for chromosomal alterations, which can lend biological insight into cancer processes. Genomes of 25 ACC clinical samples were queried on the Agilent 44K Human Genome comparative genomic hybridization array detecting regions of chromosomal gain and loss within the tumor population. Commonly shared amplifications appearing in z50% of tumors at P V 10 À4 include regions within chromosomes 5, 7, 12, 16q, and 20. Deleted genomic regions within ACC include portions of chromosomes 1, 3p, 10q, 11, 14q, 15q, 17, and 22q. Genomic aberrations in regions associated with differential survival (P V 0.05) and presence in z20% of tumors include amplifications of 6q, 7q, 12q, and 19p. Deletions within stratified survival groups include localized regions within 3, 8, 10p, 16q, 17q, and 19q. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation-dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. [Mol Cancer Ther 2008;7(2):425 -31]

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).…”

“…These included 87 ACA and 124 ACC samples (Supplementary Table 3). The CGH data set presented by Stephan et al (2008) was accessible at GEO, and these samples were reclassified and reanalysed by applying DNA Analytics software (version 4.0.85, Agilent Technologies, Santa Clara, CA, USA).…”

“…Gain of chr19q12 has already been described (Supplementary Table 3 Table 3). Stephan et al (2008) reported a 391 kb-long segment on chr12q13.2 that correlated with poor survival, CDK2 is one of the B25 genes mapped to this chromosome segment.…”

Single nucleotide polymorphism array profiling of adrenocortical tumors: evidence for an adenoma carcinoma sequence?

“…Copy number alterations (CNAs) have also been described in adrenal hyperplasia, ACA and ACC using fluorescence in situ hybridization (FISH), karyotyping, and either conventional comparative genomic hybridization (CGH) [19,20,21,22,23,24,25] or array-based CGH [23,26,27]. In particular, losses at 1p, 2q, 3p, 6q, 9, 11, 17p, and 18q and gains at 4, 5, 12q, 16, 19 and 20q have been reported in patients with sporadic ACC, some of them being associated with a poor prognosis [28].…”

ENDOCRINE TUMOURS: The genomics of adrenocortical tumors

“…Finally the ACC genome tends to be altered compared with ACA, with extended chromosomal gains, losses and losses of heterozygosity in a majority of ACC (60,61,62,63).…”