Supplementary Figures S1-S22 from Integrative Analysis of a Large Real-World Cohort of Small Cell Lung Cancer Identifies Distinct Genetic Subtypes and Insights into Histologic Transformation

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Figure S1: Patterns of tumor mutational burden across different ancestry groups. Figure S2: Spectrum of TP53 and RB1 mutations in SCLC. Figure S3: Gene alteration landscape detected from targeted sequencing of liquid biopsies. Figure S4: Chromosomal loss events are frequent in SCLC and are preferentially enriched for tumor suppressor genes. Figure S5: Hematoxylin & Eosin (H&E) staining for some representative SCLC tumors with rare genomic alterations. Figure S6: Gene alterations detected in SMARCA4-altered SCLC. Figure S7: SCLC tumors exhibit recurrent gene rearrangements with therapeutic potential. Figure S8: Trends of overall survival across different ancestry groups and stage in the clinical cohort. Figure S9: Examination of tumor purity and tumor mutational burden (TMB). Figure S10: Liver and Brain SCLC metastases are enriched for chromosomal arm-level gains compared to lung-biopsied SCLC tumors. Figure S11: SCLC tumors present with unique co-occurring and mutual exclusive patterns of gene alterations. Figure S12: SCLC tumors with wild-type TP53 and/or RB1 have a low tumor mutational burden. Figure S13: SCLC tumors with wild-type TP53 and/or RB1 present with specific gene alterations. Figure S14: A smoking-associated mutational signature is rare in TP53/RB1 WT SCLC tumors. Figure S15: TP53 and RB1 alterations are less frequent in never smokers. Figure S16: Patterns of overall survival based on TP53 and RB1 alteration status. Figure S17: TP53 and RB1 mutations are more frequent in older patients with SCLC. Figure S18: Gene alterations detected in HPV-positive SCLC. Figure S19: Examination of HPV subtypes and prevalence in TP53/RB1 mutant and wild-type SCLC tumors. Figure S20: EGFR-mutant SCLC tumors exhibit unique mutational signature profiles. Figure S21: No overall survival differences based on EGFR mutation status in SCLC. Figure S22: Putative transformed SCLC tumors from EGFR-mutant NSCLC are enriched for EGFR exon 19 deletions.

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