Chromosome structural variation in tumorigenesis: mechanisms of formation and carcinogenesis
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Epigenetics & Chromatin Open Access
REVIEW
Chromosome structural variation in tumorigenesis: mechanisms of formation and carcinogenesis Wen‑Jun Wang , Ling‑Yu Li and Jiu‑Wei Cui*
Abstract With the rapid development of next-generation sequencing technology, chromosome structural variation has gradu‑ ally gained increased clinical significance in tumorigenesis. However, the molecular mechanism(s) underlying this structural variation remain poorly understood. A search of the literature shows that a three-dimensional chromatin state plays a vital role in inducing structural variation and in the gene expression profiles in tumorigenesis. Struc‑ tural variants may result in changes in copy number or deletions of coding sequences, as well as the perturbation of structural chromatin features, especially topological domains, and disruption of interactions between genes and their regulatory elements. This review focuses recent work aiming at elucidating how structural variations develop and misregulate oncogenes and tumor suppressors, to provide general insights into tumor formation mechanisms and to provide potential targets for future anticancer therapies. Keywords: Structural variation, Cancer, Translocation, Chromothripsis Introduction Widespread chromosomal genomic rearrangement and point mutations are underlying hallmarks of the cancer genome. Next-generation sequencing technology has enabled the detection of diverse patterns of genomic changes in human somatic cells. Chromosome structural variation, a vital kind of somatic mutation, is involved in the process of genomic rearrangement ranging from genes to entire chromosomes, and also affects gene expression regulation. Chromosome structural variation is a vital driver of oncogenesis and progression in both solid tumors and hematopoietic malignancies [1]. The combination of clinical features and structural variations provides the opportunity for cancer diagnosis, reasonable tumor subtype classification, prognosis, and precision treatment [2]. In fact, clinical testing for specific *Correspondence: [email protected] Cancer Center, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin, China
mutations and genomic classification has achieved overwhelming successes in hematology [2]. With the development of molecular biology techniques, many specific chromosomal structural variations (e.g., TMPRSS2-ERG and EML4-ALK) have also been identified in solid tumors in recent years. The Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) collaborated to analyze structural variants, genomic breakpoint cluster regions, and gene expression based on whole-genome sequencing data from 2658 cancers patients across 38 tumor types [3, 4]. However, our understanding of the underlying molecular mechanisms of structural variation remains incomplete. Nonetheless, accumulating evidence suggests that changes in the three-dimensional (3D) conformational composition or topolo
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