Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
Copyright policy )Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.
- University of California, San Francisco United States
- UNC Lineberger Comprehensive Cancer Center United States
- University of Michigan–Flint United States
- Brown University United States
- UNIVERSIDADE DE SAO PAULO Brazil
Adult, Male, Outcome Assessment, Adolescent, Oncology and Carcinogenesis, Bioinformatics and Computational Biology, 610, Cancer Genome Atlas Research Network, Disease-Free Survival, Young Adult, Rare Diseases, Clinical Research, Outcome Assessment, Health Care, Genetics, 80 and over, Adrenocortical Carcinoma, Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Child, Cancer, Aged, Aged, 80 and over, Neoplastic, Genome, Biomedical and Clinical Sciences, Genome, Human, Gene Expression Profiling, Human Genome, Neurosciences, Genomics, Biological Sciences, DNA Methylation, Middle Aged, Prognosis, Adrenal Cortex Neoplasms, 4.1 Discovery and preclinical testing of markers and technologies, Health Care, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Biochemistry and cell biology, Mutation, Female, Biotechnology, Human
Adult, Male, Outcome Assessment, Adolescent, Oncology and Carcinogenesis, Bioinformatics and Computational Biology, 610, Cancer Genome Atlas Research Network, Disease-Free Survival, Young Adult, Rare Diseases, Clinical Research, Outcome Assessment, Health Care, Genetics, 80 and over, Adrenocortical Carcinoma, Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Child, Cancer, Aged, Aged, 80 and over, Neoplastic, Genome, Biomedical and Clinical Sciences, Genome, Human, Gene Expression Profiling, Human Genome, Neurosciences, Genomics, Biological Sciences, DNA Methylation, Middle Aged, Prognosis, Adrenal Cortex Neoplasms, 4.1 Discovery and preclinical testing of markers and technologies, Health Care, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Biochemistry and cell biology, Mutation, Female, Biotechnology, Human
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