Extended Data Fig. 11: ATRX mutation correlates with iCMS3 transcriptional subtype.
From: Loss of colonic fidelity enables multilineage plasticity and metastasis
(a) Summary data indicating presence or absence of ATRX mutation in iCMS2 vs iCMS3 transcriptional subtypes. Data extracted from TCGA dataset. Number of tumours in each group indicated on graph, n = 348 vs 244 tumours. (b) Heatmap clustering of Marisa CRC patient dataset of 557 tumours based on squamous-like (AtrxKO) and colonic epithelial (AtrxWT) gene expression signatures. (c) Percentage of tumours located in the distal (left sided) or proximal (right sided) colon in different Atrx expression clusters. One-tailed Chi-squared test, p value = 1.72e-16. (d) MMR status of tumours in HiCol, Intermediate and HiSquam expression clusters. (e) Mutational status of tumours in HiCol, Intermediate and HiSquam expression clusters. (f) TNM stage of tumours in HiCol, Intermediate and HiSquam expression clusters. (g) Correlation of AtrxWT (colonic epithelial-like) and AtrxKO (squamous-like) gene expression signatures in GSE39582 dataset. iCMS status overlayed in purple (iCMS2) and orange (iCMS3). (h) Percentage of tumours designated as iCMS2 (i2) or iCMS3 (i3) transcriptional subtype in different Atrx expression clusters. Chi-squared test, p value = 2.2e-16. (i) FACS plots for analysing EPCAM+ve/LY6D+ve cells from normal colon and colon cancer samples. Box highlights the presence of EPCAM+ve/LY6D+ve cells. (j) Quantification of EPCAM+ve/LY6D+ve cells from normal colon and colon cancer samples, separated into left and right sided groups. For (a) p value was calculated using two-sided Fisher’s exact test. For (c), (d), (e), (f) and (h) p values were calculated using one-tailed Chi-Square test. For (g) Pearson’s correlation coefficient and two-sided p-value are described. The blue line and gray shaded area represent the regression line and 95% confidence interval. For (j) n = 5 (normal colon), n = 2 (left sided tumour), n = 3 (right sided tumour) biological independent samples. Data are mean ± SD. P values were calculated using ordinary one-way ANOVA with multiple comparisons.
