title: Shared and unique mutational gene co-occurrences in cancers.
abstract: Cancers are often associated with mutations in multiple genes; thus, studying the distributions of genes that harbor cancer-promoting mutations in cancer samples and their co-occurrences could provide insights into cancer diagnostics and treatment. Using data from the Catalogue of Somatic Mutations in Cancer (COSMIC), we found that mutated genes in cancer samples followed a power-law distribution. For instance, a few genes were mutated in a large number of samples (designated as high-frequent genes), while a large number of genes were only mutated in a few samples. This power-law distribution can be found in samples of all cancer types as well as individual cancers. In samples where two or more mutated genes are found, the high-frequent genes, i.e., those that were frequently mutated, often did not co-occur with other genes, while the other genes often tended to co-occur. Co-occurrences of mutated genes were often unique to a certain cancer; however, some co-occurrences were shared by multiple cancer types. Our results revealed distinct patterns of high-frequent genes and those that were less-frequently mutated in the cancer samples in co-occurring and anti-co-occurring networks. Our results indicated that distinct treatment strategies should be adopted for cancer patients with known high-frequent gene mutations and those without. The latter might be better treated with a combination of drugs targeting multiple genes. Our results also suggested that possible cross-cancer treatments, i.e., the use of the same drug combinations, may treat cancers of different histological origins.
authors: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: Junqi.Liu@medma.uni-heidelberg.de.
authors: Junqi
authors: J
authors: Liu
authors: The Institute of Experimental and Clinical Pharmacology and Toxicology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: di.zhao@medma.uni-heidelberg.de.
authors: Di
authors: D
authors: Zhao
authors: Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: fanruitai@126.com.
authors: Ruitai
authors: R
authors: Fan
mesh_terms: D004260:DNA Repair / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D005787:Gene Frequency; D053263:Gene Regulatory Networks; D016147:Genes, Tumor Suppressor; D018816:Genes, cdc; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes
keywords: Cancer treatment; Gene mutation; Mutation frequency; Network