Abstract 5172: Whole exome mutation landscape of 70 commonly used colorectal cancer cell lines

Abstract Human colorectal cancer (CRC) cell lines are an important model system for studying the biology of this malignancy as well as therapeutic and biomarker discovery. However, data on the degree to which established CRC cell lines reflect the somatic diversity of primary cancers at the genome level are limited. Using whole exome sequencing and SNP microarray analysis we show that the profile of mutations and DNA copy-number alterations in 70 widely-used CRC cell lines closely resembles that of primary colorectal tumors published by The Cancer Genome Atlas Network. We demonstrate presence of at least two hypermutation phenotypes, consistent with defective DNA mismatch repair and DNA polymerase epsilon (POLE) proof-reading deficiency, and similar mutation signatures in the WNT, MAPK, PI3K, TGF-beta and TP53 pathways. Paired cell lines derived from the same tumor are found to exhibit substantial mutation and DNA copy-number differences, with in silico simulations suggesting that these largely reflect pre-existing tumor cell heterogeneity, but these differences do not obscure known driver genes. Our genome level data indicate that CRC cell lines are representative models of the main molecular subtypes of primary tumors, and will facilitate informed selection of molecularly-defined models for preclinical investigations. Citation Format: Oliver Sieber, Dmitri Mouradov, Clare Sloggett, Robert Jorissen, Chris Love, Shan Li, Antony Burgess, Diego Arango, Robert Strausberg, Daniel Buchanan, Samuel Wormald, Liam O'Connor, Jenny Wilding, David Bicknell, Ian Tomlinson, Walter Bodmer, John Mariadason. Whole exome mutation landscape of 70 commonly used colorectal cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5172. doi:10.1158/1538-7445.AM2014-5172