title: Mutated Fanconi anemia pathway in non-Fanconi anemia cancers.
abstract: An extremely high cancer incidence and the hypersensitivity to DNA crosslinking agents associated with Fanconi Anemia (FA) have marked it to be a unique genetic model system to study human cancer etiology and treatment, which has emerged an intense area of investigation in cancer research. However, there is limited information about the relationship between the mutated FA pathway and the cancer development or/and treatment in patients without FA. Here we analyzed the mutation rates of the seventeen FA genes in 68 DNA sequence datasets. We found that the FA pathway is frequently mutated across a variety of human cancers, with a rate mostly in the range of 15 to 35 % in human lung, brain, bladder, ovarian, breast cancers, or others. Furthermore, we found a statistically significant correlation (p < 0.05) between the mutated FA pathway and the development of human bladder cancer that we only further analyzed. Together, our study demonstrates a previously unknown fact that the mutated FA pathway frequently occurs during the development of non-FA human cancers, holding profound implications directly in advancing our understanding of human tumorigenesis as well as tumor sensitivity/resistance to crosslinking drug-relevant chemotherapy.
authors.affiliation: Program of Cancer Biology, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI, USA.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Program of Cancer Biology, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI, USA.
authors.forename: Yuan-Hao
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Program of Cancer Biology, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI, USA.
authors.forename: Jayabal
authors.initials: J
authors.lastname: Panneerselvam
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Program of Epidemiology, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI, USA.
authors.forename: Lenora W M
authors.initials: LW
authors.lastname: Loo
authors.affiliation: Program of Cancer Biology, University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI, USA.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Fei
mesh_terms: D063646:Carcinogenesis; D045744:Cell Line, Tumor; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male
keywords: Fanconi anemia genes; TCGA; cancer treatment; the mutated FA pathway; tumorigenesis