[PMID:27732578] [Nature]

A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns

Chromothripsis and polyploidizationin Pancreatic Cancer.  “To evaluate polyploidization, we developed and validated a new informatic tool, termed CELLULOID, which estimates tumour ploidy and copy number from whole-genome data.” “We developed a sensitive algorithm, termed ChromAL, to differentiate chromothripsis from localized gradual events that accumulate over time.” BOth CELLULOID and ChromAL are implemented in R. “Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory.”


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