Extended Data Fig. 1: Genomic landscape of the Beat AML cohort.
From: Functional genomic landscape of acute myeloid leukaemia
In total, 622 specimens from 531 patients were used for whole-exome sequencing. Automated and manual curation steps (described in the Methods, Supplementary Information and at http://vizome.org/additional_figures_BeatAML.html) were used to obtain a final set of high-confidence variants (annotated in Supplementary Table 7) and the earliest sample for each individual patient was used in this analysis. Clinical cytogenetics and gene fusion calls from RNA sequencing were used to curate recurrent gene rearrangements (Supplementary Information). The mutational profile for each patient is shown for frequency-ranked mutational events (top) and frequency-ranked gene rearrangements (bottom). The mosaic plot is annotated with clinical features of each case, such as diagnosis or relapse and de novo or transformed disease states, and the first bar chart on the right summarizes the cohort frequencies of mutational and gene rearrangement events. The last bar chart on the right summarizes the frequency of significant drug–mutation associations for the given gene across the cohort with drug sensitivity displayed in red and drug resistance displayed in blue. Eleven genes that have not previously been reported to be somatically mutated in cancer were observed with mutations at approximately 1% cohort frequency: CUB and Sushi multiple domains 2 (CSMD2), NAC alpha domain containing (NACAD), teneurin transmembrane protein 2 (TENM2), aggrecan (ACAN), ADAM metallopeptidase with thrombospondin type 1 motif 7 (ADAMTS7), immunoglobulin-like and fibronectin type III domain containing 1 (IGFN1), neurobeachin-like 2 (NBEAL2), poly(U) binding splicing factor 60 (PUF60), zinc-finger protein 687 (ZNF687), cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2) and glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B). For the number of samples used to correlate each drug with mutations, see Supplementary Table 17.
