When Genome Maintenance Goes Badly Awry.
Genetic abnormalities are present in all tumor types, although the frequency and type can vary. Chromosome abnormalities include highly aberrant structures, particularly chromothriptic chromosomes. The generation of massive sequencing data has illuminated the scope of the mutational burden in cancer genomes, identifying patterns of mutations (mutation signatures), which have the potential to shed light on the relatedness and etiologies of cancers and impact therapy response. Some mutation patterns are clearly attributable to disruptions in pathways that maintain genomic integrity. Here we review recent advances in our understanding of genetic changes occurring in cancers and the roles of genome maintenance pathways.
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Elizabeth M
EM
Kass
Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Mary Ellen
ME
Moynahan
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. Electronic address: m-jasin@ski.mskcc.org.
Maria
M
Jasin
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations; D000072837:Chromothripsis; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D010641:Phenotype; D059467:Transcriptome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004247:DNA
BRCA1; BRCA2; Cancer genomes; chromothripsis; homologous recombination; kataegis; mutation signature