Chromosome–Breakage Genome Instability and Chromothripsis in Breast Cancer
The array comparative genomic hybridization (aCGH) analysis is usually performed to clarify regional gain, amplification and deletion of chromosomes. In the present study, the authors focused on the putative chromosomal breakpoints that can cause gene rearrangements by the method combining cell sorting and aCGH and assessed the total number of putative breakpoints per genome, designated as breakpoint instability index (BPI) by using Agilent’s ADM-2 algorithm. Although aCGH is not very novel technology, the trial to assay chromosomal breakpoints is timely when the concept of chromothripsis is going to be prevailing. Chromothripsis is a form of complex catastrophic chromosome rearrangement, discovered from whole-genome sequencing and defined from four hallmarks – alternating copy number profiles, loss and preservation of heterozygosity, pairing of the breakpoint ends, and clustering of rearrangements [Citation1]. The authors at first documented the prevalence of chromothripsis in breast cancer. Chromothripsis affected various chromosomes in 41% of high-risk tumors. Clinical implication of this phenomenon remains undetermined.
Chromothripsis and Beyond: Rapid Genome Evolution from Complex Chromosomal Rearrangements
Recent technologies of comprehensive genome analyses have discovered a new classes of complex catastrophic chromosomal rearrangement: chromothripsis [Citation2], chromoanasynthesis [Citation3], and chromoplexy [Citation4]. They appear to originate from single events that involve hundreds of rearrangements and DNA copy number changes, which is against conventional multistage carcinogenesis models if these classes are key mechanisms for cancer evolution. Chromothripsis sometimes is certainly a mechanism to form high-level gene amplifications and, rarely, oncogenic translocations. However, disruption of chromosomal integrity in chromothripsis and chromoanasynthesis should be generally deleterious to the cell, and their breakpoints are clustered in a highly localized manner. Furthermore, the event similar to chromothripsis is reported to occur constitutionally in some patients with congenital developmental disorders. Chromoplexy is characterized by chain translocations involving multiple chromosomes, and unstable chromosomes whereby generated may result in additional chromothripsis. The true incidence of these complex chromosomal rearrangements and their association with molecular carcinogenesis are under investigation.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
References
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