Integrated genomic characterization of adrenocortical carcinoma
Copyright policy )Integrated genomic characterization of adrenocortical carcinoma
Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland. Despite overall poor prognosis, ACC outcome is heterogeneous. We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase, was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the β-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.
- Sorbonne Paris Cité France
- Institut Gustave Roussy France
- Inserm France
- Paris 13 University France
- University of Western Brittany France
Adult, Male, Adolescent, DNA Mutational Analysis, 610, Loss of Heterozygosity, Cohort Studies, Young Adult, SDG 3 - Good Health and Well-being, Ubiquitin-Protein Ligases/metabolism, 80 and over, Adrenocortical Carcinoma, MicroRNAs/metabolism, Humans, Exome, Polymorphism, Aged, Aged, 80 and over, Neoplastic, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adolescent, Adrenal Cortex Neoplasms; genetics, Adrenocortical Carcinoma; genetics, Adult, Aged, Aged; 80 and over, Cohort Studies, DNA Methylation, DNA Mutational Analysis, Exome, Female, Gene Expression Profiling, Gene Expression Regulation; Neoplastic, Genomics, Humans, Loss of Heterozygosity, Male, MicroRNAs; metabolism, Middle Aged, Multigene Family, Mutation, Polymorphism; Single Nucleotide, Prognosis, Telomere; ultrastructure, Ubiquitin-Protein Ligases; metabolism, Young Adult, beta Catenin; metabolism, Gene Expression Profiling, Single Nucleotide, Genomics, EMC MM-03-24-01, DNA Methylation, Middle Aged, Prognosis, beta Catenin/metabolism, Telomere/ultrastructure, Adrenal Cortex Neoplasms, Gene Expression Regulation, Neoplastic, Adrenal Cortex Neoplasms/*genetics, MicroRNAs, Gene Expression Regulation, adolescent, Multigene Family, Mutation, Female, Adrenocortical Carcinoma/*genetics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Adult, Male, Adolescent, DNA Mutational Analysis, 610, Loss of Heterozygosity, Cohort Studies, Young Adult, SDG 3 - Good Health and Well-being, Ubiquitin-Protein Ligases/metabolism, 80 and over, Adrenocortical Carcinoma, MicroRNAs/metabolism, Humans, Exome, Polymorphism, Aged, Aged, 80 and over, Neoplastic, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adolescent, Adrenal Cortex Neoplasms; genetics, Adrenocortical Carcinoma; genetics, Adult, Aged, Aged; 80 and over, Cohort Studies, DNA Methylation, DNA Mutational Analysis, Exome, Female, Gene Expression Profiling, Gene Expression Regulation; Neoplastic, Genomics, Humans, Loss of Heterozygosity, Male, MicroRNAs; metabolism, Middle Aged, Multigene Family, Mutation, Polymorphism; Single Nucleotide, Prognosis, Telomere; ultrastructure, Ubiquitin-Protein Ligases; metabolism, Young Adult, beta Catenin; metabolism, Gene Expression Profiling, Single Nucleotide, Genomics, EMC MM-03-24-01, DNA Methylation, Middle Aged, Prognosis, beta Catenin/metabolism, Telomere/ultrastructure, Adrenal Cortex Neoplasms, Gene Expression Regulation, Neoplastic, Adrenal Cortex Neoplasms/*genetics, MicroRNAs, Gene Expression Regulation, adolescent, Multigene Family, Mutation, Female, Adrenocortical Carcinoma/*genetics, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
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