Extended Data Fig. 1: Functional genomic screening identifies that MSI cancers are selectively dependent on WRN.
From: WRN helicase is a synthetic lethal target in microsatellite unstable cancers
a, Screened cell lines plotted by number of deletions and fraction of deletions occurring in microsatellite (MS) regions. Genes involved in MMR that are lost are indicated by different colours. None, no predicted loss of MMR genes. Multiple, loss of more than one MMR gene. n/a, not available. b, Using PCR-based MSI phenotyping, P values (empirical Bayes moderated t-test) were plotted against the mean difference of dependency scores between MSI and MSS cell lines for Achilles (n = 19 MSI; n = 291 MSS) and DRIVE (n = 23 MSI; n = 252 MSS). c, Dependency scores for each RecQ helicase plotted for MSI and MSS cell lines from Achilles (n = 32 MSI; n = 413 MSS) and DRIVE (n = 38 MSI; n = 337 MSS). Q values (Wilcoxon rank-sum test) for Achilles/DRIVE are 5.0 × 10−8/1.7 × 10−8, 0.73/0.52, 0.73/0.85, 0.25/0.73 and 0.08/not available for WRN, RECQL, BLM, RECQL5 and RECQL4, respectively. Centre lines indicate medians. Boxes indicate 25th and 75th percentiles; whiskers extend to 1.5× IQR beyond the box and individual data points are represented by dots. d, Sensitivity and positive predictive value of indicated relationship between biomarker and genetic dependency. e, Dependency score distributions and associated biomarkers for example biomarker–genetic dependency relationships. Width of coloured regions represent density estimates. Horizontal dashed line: threshold used to separate dependent and non-dependent cell lines. n = 37, 14, 541 MSI cell lines from typical lineage, MSI cell lines from atypical lineage, MSS cell lines, respectively. n = 120/546 KRAS hotspot mutants/other; 65/601 BRAF hotspot mutants/other; 86/580 PIK3CA hotspot mutants/other.
