Extended Data Fig. 8: TRACERx 421 immune and genomic data. | Nature

Extended Data Fig. 8: TRACERx 421 immune and genomic data.

From: Clonal driver neoantigen loss under EGFR TKI and immune selection pressures

Extended Data Fig. 8: TRACERx 421 immune and genomic data.

a, Comparison of histological tumour infiltrating lymphocyte (TIL) scores of the RUL and liver metastasis with primary tumours from the TRACERx 421 cohort (invasive adenocarcinoma n = 232, Squamous cell carcinoma n = 131, Other histology n = 46). b, Comparison of TIL scores with EGFR-mutant NSCLC cases within the TRACERx 421 cohort (n = 28). c, Using CIBERSORTx, the proportion of immune cells in all regions of the EGFR-mutant TRACERx 421 cohort with RNASeq data was calculated using the LM22 signature. The right upper lobe (RUL) and liver metastasis from this case are represented with dotted lines (blue and red, respectively). A solid black line represents the median of the EGFR-mutant TRACERx 421 tumours (n = 23 EGFR-mutant cases, with 54 primary tumour samples, 4 of which are metastatic). d, Illusion of clonality from single region biopsies; variants can appear to be clonal when they are in fact subclonal at the tumour level. e, Mutation heatmap for biopsies shown in panel. Whole-genome doubling (WGD) is usually an early clonal event in NSCLC, therefore, pre-WGD are likely to also be clonal. f, Mutations occurring post-WGD can be lost more easily than pre-WGD mutations through chromosomal instability as they occur on 1 chromosome. g, Mutations occurring pre-WGD, were more likely to be found in every metastasis sequenced than post-WGD mutations (96.7% versus 25.3%). h, Summary of clonal lung cancer driver gene SNV or DNV mutations timed relative to WGD. This only has genes with at least five mutations in the TRACERx 421 cohort. Top panel represents the number of mutations; lower panel represents the proportions of the variants in that gene. Dark red represents post-WGD, grey represents unclear timing & dark blue represents pre-WGD. WGD = whole genome doubling; RUL = Right upper lobe. Illustrations in df were created using BioRender (https://biorender.com).

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