title: Mechanisms and Consequences of Cancer Genome Instability: Lessons from Genome Sequencing Studies.
abstract: During tumor evolution, cancer cells can accumulate numerous genetic alterations, ranging from single nucleotide mutations to whole-chromosomal changes. Although a great deal of progress has been made in the past decades in characterizing genomic alterations, recent cancer genome sequencing studies have provided a wealth of information on the detailed molecular profiles of such alterations in various types of cancers. Here, we review our current understanding of the mechanisms and consequences of cancer genome instability, focusing on the findings uncovered through analysis of exome and whole-genome sequencing data. These analyses have shown that most cancers have evidence of genome instability, and the degree of instability is variable within and between cancer types. Importantly, we describe some recent evidence supporting the idea that chromosomal instability could be a major driving force in tumorigenesis and cancer evolution, actively shaping the genomes of cancer cells to maximize their survival advantage.
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea; email: junekoo_lee@kaist.ac.kr.
authors.forename: June-Koo
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul 06351, South Korea; email: yla.choi@samsung.com.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.|Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; email: mijung_kwon@dfci.harvard.edu.
authors.forename: Mijung
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115; email: peter_park@hms.harvard.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
keywords: aneuploidy; cancer evolution; chromosomal instability; chromosomal rearrangement; hypermutation; microsatellite instability