title: Tumor Suppressor Genes within Common Fragile Sites Are Active Players in the DNA Damage Response.
abstract: The role of common fragile sites (CFSs) in cancer remains controversial. Two main views dominate the discussion: one suggests that CFS loci are hotspots of genomic instability leading to inactivation of genes encoded within them, while the other view proposes that CFSs are functional units and that loss of the encoded genes confers selective pressure, leading to cancer development. The latter view is supported by emerging evidence showing that expression of a given CFS is associated with genome integrity and that inactivation of CFS-resident tumor suppressor genes leads to dysregulation of the DNA damage response (DDR) and increased genomic instability. These two viewpoints of CFS function are not mutually exclusive but rather coexist; when breaks at CFSs are not repaired accurately, this can lead to deletions by which cells acquire growth advantage because of loss of tumor suppressor activities. Here, we review recent advances linking some CFS gene products with the DDR, genomic instability, and carcinogenesis and discuss how their inactivation might represent a selective advantage for cancer cells.
authors.affiliation: Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Idit
authors.initials: I
authors.lastname: Hazan
authors.affiliation: Cellular Senescence Group, Department of Epigenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hofmann
authors.affiliation: Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.|Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.|Department of Biochemistry, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Rami I
authors.initials: RI
authors.lastname: Aqeilan
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D043283:Chromosome Fragile Sites / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D016147:Genes, Tumor Suppressor; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology