Supplementary Figures S1-S6 from Molecular Characterization of Endometrial Carcinomas in Black and White Patients Reveals Disparate Drivers with Therapeutic Implications

Abstract

<p>Supplementary Figure S1. Consort diagram summarizing the endometrial cancer patients included in this study. Endometrial carcinomas subjected to clinical tumor-normal MSK-IMPACT sequencing that had low tumor purity, no somatic mutations, upon re-review were not of uterine origin, could not be classified into a molecular subtype or duplicates (i.e., two samples from the same patient) were excluded. Supplementary Figure S2. Histologic and molecular subtype distribution of primary and recurrent/metastatic endometrial cancers in self-identified Black and White patients. A, Distribution of histologic subtypes of primary (top) and recurrent/metastatic (bottom) endometrial carcinomas (ECs) in self-identified Black and White patients. P-value, Pearson’s Chi-squared test. B, Distribution of molecular subtypes of primary (top) and recurrent/metastatic (bottom) ECs in Black and White patients, subjected to clinical MSK-IMPACT sequencing. P-value, Pearson’s Chi-squared test. CNH/TP53abn, copy number-high/TP53 abnormal; CN-L/NSMP, copy number-low/no specific molecular profile; G1/2, tumor grades 1 and 2; G3, grade 3; MSI-H, microsatellite instability-high; NOS, not otherwise specified. Supplementary Figure S3. Histologic subtypes and molecular features by Ashkenazi Jewish (ASJ) genetic ancestry of endometrial carcinomas from this study. A, ASJ genetic ancestry inference based on MSK-IMPACT sequencing data (as described in Arora et al, Cancer Discov 2022) of self-reported White endometrial cancer (EC) patients included in this study. B, Histologic subtype (left) and molecular subtypes (right) in self-identified White EC patients of ASJ and of non-ASJ genetic ancestry. P-value, Pearson’s Chi-squared test. ns, not significant. CN-H/TP53abn, copy number-high/TP53 abnormal; CN-L/NSMP, copy number-low/no specific molecular profile; G1/2, tumor grades 1 and 2; G3, grade 3; MSI-H, microsatellite instability-high; NOS, not otherwise specified. Supplementary Figure S4. Histologic types and molecular features by genetic ancestry of endometrial carcinomas from TCGA and from this study. A, Genetic ancestry inference of self-reported Black endometrial cancer (EC) patients included in the pan-cancer TCGA study (Hoadley et al, Cell 2018; Carrott-Zhang et al, Cancer Cell 2020). B, Histologic subtype (left) and molecular subtypes (right) in self-identified Black EC patients of African genetic ancestry and of Admixed genetic ancestry from TCGA. ns, not significant, Pearson’s Chi-squared test. CN-H/TP53abn, copy number-high/TP53 abnormal; CN-L/NSMP, copy number-low/ no specific molecular profile; G1/2, tumor grades 1 and 2; G3, grade 3; MSI-H, microsatellite instability-high; NOS, not otherwise specified. C, Tumor mutational burden (TMB, left) and fraction of genome altered (right) in ECs by genetic ancestry inference from the current study. ns, not significant, Mann-Whitney U test. Mut/Mb, number of mutations per megabase. Supplementary Figure S5. Tumor mutational burden and chromosomal instability in endometrial carcinomas by tissue type and molecular subtype in self-identified Black and White patients. A, Tumor mutational burden (TMB) and fraction of genome altered of primary (top) and recurrent/ metastatic endometrial carcinomas (ECs) subjected to clinical tumor-normal MSK-IMPACT sequencing in Black and White patients. B, TMB of ECs in Black and White patients by molecular subtypes. C, Fraction of genome altered (FGA) of ECs occurring in Black and White patients by molecular subtype. CN-H/TP53abn, copy number-high/TP53 abnormal; CN-L/NSMP, copy number-low/no specific molecular profile; MSI-H, microsatellite instability-high. Mut/Mb, number of mutations per megabase. ****, p<0.0001; ***, p<0.001, **, p<0.01, *, p<0.05; ns, not significant. Mann-Whitney U test. TMB outliers are not graphically represented in the plots. Due to limited numbers, statistical analysis for the POLE group was not performed. Supplementary Figure S6. Mutually exclusive and co-occurring genetic alterations in endometrial carcinomas. Mutually exclusive and co-occurring genetic alterations (pathogenic mutations and copy number alterations) in endometrial carcinomas (ECs) displayed as a triangular matrix. Mutual exclusivity and cooccurrence analyses was performed using combinations of mutually exclusive alterations (CoMEt) with the use of a pair-wise Fisher’s exact test to detect the presence of significant pairs of genes. Blue indicates tendency toward co-occurrence, whereas red indicates tendency toward exclusiveness. A, All ECs included in the study. B, ECs from self-identified Black patients. C, ECs from self-identified White patients. *, p<0.01; ×, p<0.05.</p>