Case-oriented pathways analysis in pancreatic adenocarcinoma using data from a sleeping beauty transposon mutagenesis screenReportar como inadecuado




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BMC Medical Genomics

, 9:16

First Online: 01 April 2016Received: 20 January 2015Accepted: 09 March 2016

Abstract

BackgroundMutation studies of pancreatic ductal adenocarcinoma PDA have revealed complicated heterogeneous genomic landscapes of the disease. These studies cataloged a number of genes mutated at high frequencies, but also report a very large number of genes mutated in lower percentages of tumors. Taking advantage of a well-established forward genetic screening technique, with the Sleeping Beauty SB transposon, several studies produced PDA and discovered a number of common insertion sites CIS and associated genes that are recurrently mutated at high frequencies. As with human mutation studies, a very large number of genes were found to be altered by transposon insertion at low frequencies. These low frequency CIS associated genes may be very valuable to consider for their roles in cancer, since collectively they might emerge from a core group of genetic pathways.

ResultIn this paper, we determined whether the genetic mutations in SB-accelerated PDA occur within a collated group of biological processes defined as gene sets. The approach considered both genes mutated in high and lower frequencies. We implemented a case-oriented, gene set enrichment analysis CO-GSEA on SB altered genes in PDA. Compared to traditional GSEA, CO-GSEA enables us to consider individual characteristics of mutation profiles of each PDA tumor. We identified genetic pathways with higher numbers of genetic mutations than expected by chance. We also present the correlations between these significant enriched genetic pathways, and their associations with CIS genes.

ConclusionThese data suggest that certain pathway alterations cooperate in PDA development.

KeywordsForward genetic screen Sleeping Beauty transposon Case-oriented gene set analysis Pathways correlations CIS Common insertion sites Electronic supplementary materialThe online version of this article doi:10.1186-s12920-016-0176-7 contains supplementary material, which is available to authorized users.

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Autor: Yen-Yi Ho - Timothy K. Starr - Rebecca S. LaRue - David A. Largaespada

Fuente: https://link.springer.com/



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