title: Concordance between somatic copy number loss and down-regulated expression: A pan-cancer study of cancer predisposition genes.
abstract: Cancer predisposition genes (CPGs) are a class of cancer genes in which germline variants lead to increased risk of cancer. Research has revealed that copy number variation (CNV) may be linked to cancer susceptibility in CPGs. In this pan-cancer analysis, we explored the relationship between somatic CNV and gene expression changes in CPGs. Based on curated 827 human CPGs from literature, we firstly identified 729 CPGs with precise CNV information from 5067 tumor samples using TCGA CNV data. Among them, 128 CPGs tended to have more frequent copy number losses (CNLs) compared with copy number gains (CNGs). Then by correlating these CNV data with TCGA gene expression data, we obtained 49 CPGs with concordant CNLs and gene down-regulation. Intriguingly, five CPGs showed concordance between CNL and down-regulation in 50 or more tumor samples: MTAP (216 samples), PTEN (143), MCPH1 (86), SMAD4 (63), and MINPP1 (51), which may represent the recurrent driving force for gene expression change during oncogenesis. Moreover, network analysis revealed that these 49 CPGs were tightly connected. In summary, this study provides the first observation of concordance between CNLs and down-regulation of CPGs in pan-cancer, which may help better understand the CPG biology in tumorigenesis and cancer progression.
authors.affiliation: Institute of Health Sciences, School of Computer Science and Technology, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wei
authors.affiliation: Institute of Health Sciences, School of Computer Science and Technology, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Health Sciences, School of Computer Science and Technology, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Chun-Hou
authors.initials: CH
authors.lastname: Zheng
authors.affiliation: School of Engineering, Faculty of Science, Health, Education and Engineering, University of Sunshine Coast, Maroochydore DC, Queensland, 4558, Australia.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Health Sciences, School of Computer Science and Technology, Anhui University, Hefei, Anhui 230601, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xia
mesh_terms: D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology