Identification of relevant genetic alterations in cancer using topological data analysis
Open Access
- 30 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-10
- https://doi.org/10.1038/s41467-020-17659-7
Abstract
Large-scale cancer genomic studies enable the systematic identification of mutations that lead to the genesis and progression of tumors, uncovering the underlying molecular mechanisms and potential therapies. While some such mutations are recurrently found in many tumors, many others exist solely within a few samples, precluding detection by conventional recurrence-based statistical approaches. Integrated analysis of somatic mutations and RNA expression data across 12 tumor types reveals that mutations of cancer genes are usually accompanied by substantial changes in expression. We use topological data analysis to leverage this observation and uncover 38 elusive candidate cancer-associated genes, including inactivating mutations of the metalloproteinase ADAMTS12 in lung adenocarcinoma. We show that ADAMTS12−/− mice have a five-fold increase in the susceptibility to develop lung tumors, confirming the role of ADAMTS12 as a tumor suppressor gene. Our results demonstrate that data integration through topological techniques can increase our ability to identify previously unreported cancer-related alterations.This publication has 59 references indexed in Scilit:
- RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genomeBMC Bioinformatics, 2011
- Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survivalProceedings of the National Academy of Sciences of the United States of America, 2011
- Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesisOncogene, 2010
- TheADAMTS12metalloprotease gene is epigenetically silenced in tumor cells and transcriptionally activated in the stroma during progression of colon cancerJournal of Cell Science, 2009
- Somatic mutations affect key pathways in lung adenocarcinomaNature, 2008
- Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancersProceedings of the National Academy of Sciences of the United States of America, 2008
- Characterizing the cancer genome in lung adenocarcinomaNature, 2007
- The ADAMTS12 metalloproteinase exhibits anti-tumorigenic properties through modulation of the Ras-dependent ERK signalling pathwayJournal of Cell Science, 2007
- New Variants of Malignant Glioneuronal Tumors: A Clinicopathological Study of 40 CasesNeurosurgery, 2004
- A census of human cancer genesNature Reviews Cancer, 2004