Transflip mutations produce deletions in pancreatic cancer

Alexis L. Norris, Hirohiko Kamiyama, Alvin Makohon-Moore, Aparna Pallavajjalla, Laura A. Morsberger, Kurt Lee, Denise Batista, Christine A. Iacobuzio-Donahue, Ming-Tseh Lin, Alison Klein, Ralph H Hruban, Sarah Wheelan, James Eshleman

Research output: Contribution to journalArticle


Pancreatic ductal adenocarcinoma (PDAC) is driven by the inactivation of the tumor suppressor genes (TSGs), CDKN2A (P16) and SMAD4 (DPC4), commonly by homozygous deletions (HDs). Using a combination of high density single-nucleotide polymorphism (SNP) microarray and whole genome sequencing (WGS), we fine-mapped novel breakpoints surrounding deletions of CDKN2A and SMAD4 and characterized them by their underlying structural variants (SVs). Only one third of CDKN2A and SMAD4 deletions (6 of 18) were simple interstitial deletions, rather, the majority of deletions were caused by complex rearrangements, specifically, a translocation on one side of the TSG in combination with an inversion on the other side. We designate these as "TransFlip" mutations. Characteristics of TransFlip mutations are: (1) a propensity to target the TSGs CDKN2A and SMAD4 (P

Original languageEnglish (US)
Pages (from-to)472-481
Number of pages10
JournalGenes Chromosomes and Cancer
Issue number8
StatePublished - Aug 1 2015


ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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