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Absolute quantification of somatic DNA alterations in human cancer
Open accessAbstract
We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity.
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Self-citationThe Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers
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Proteogenomic Characterization of Endometrial Carcinoma
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Self-citationLoss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway
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Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
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Self-citationComprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer
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Self-citationOrganoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies
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“Solutions fromABSOLUTEweremanually reviewed as recommended (Carter et al., 2012; Landau et al., 2013).”
BackgroundPattern discovery and cancer gene identification in integrated cancer genomic data
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Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
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Self-citationPerspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
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Self-citationSpatially confined sub-tumor microenvironments in pancreatic cancer
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DNA methylation loss in late-replicating domains is linked to mitotic cell division
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Self-citationReal-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
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Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies
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Self-citationPan-cancer deconvolution of tumour composition using DNA methylation
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Self-citationγδ T cells are effectors of immunotherapy in cancers with HLA class I defects
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EGFR Variant Heterogeneity in Glioblastoma Resolved through Single-Nucleus Sequencing
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Self-citationBreast tumours maintain a reservoir of subclonal diversity during expansion
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Big data in basic and translational cancer research
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Immuno-genomic landscape of osteosarcoma
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The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy
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A first-generation pediatric cancer dependency map
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Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
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Ploidy Variation in Fungi: Polyploidy, Aneuploidy, and Genome Evolution
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Metadata
- Authors
- Carter, S. L., Cibulskis, K., Helman, E., McKenna, A., Shen, H., Zack, T., Laird, P. W., Onofrio, R. C., Winckler, W., Weir, B. A., Beroukhim, R., Pellman, D., Levine, D. A., Lander, E. S., Meyerson, M., & Getz, G.
- Venue
- Nature Biotechnology
- Published
- 2012-04-29
- Volume
- 30
- Issue
- 5
- Pages
- 413-421
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2170490448
- Cited by
- 2,053
- References
- 16
- FWCI
- 25.83
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
