Adrenocortical carcinoma survival rates correlated to genomic copy number variants.
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 > or =50% of tumors at P < or = 10(-4) 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 < or = 0.05) and presence in > or =20% 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.
Stephan
Elizabeth A
EA
Genetic Basis of Human Disease Division, Translational Genomics Research Institute, 445 North 5th Street, Phoenix, AZ 85004, USA. estephan@tgen.org
Chung
Tae-Hoon
TH
Grant
Clive S
CS
Kim
Seungchan
S
Von Hoff
Daniel D
DD
Trent
Jeffrey M
JM
Demeure
Michael J
MJ
D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D018268:Adrenocortical Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D002881:Chromosomes, Human, Pair 12; D002888:Chromosomes, Human, Pair 19; D002896:Chromosomes, Human, Pair 6; D002897:Chromosomes, Human, Pair 7; D018628:Gene Dosage; D006801:Humans; D008297:Male; D011379:Prognosis; D016019:Survival Analysis