American Association for Cancer Research
cd-22-0620_supplementary_tables_s1-s24_suppst1.xlsx (1.14 MB)

Supplementary Tables S1-S24 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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posted on 2023-07-07, 08:20 authored by Smruthy Sivakumar, Jay A. Moore, Meagan Montesion, Radwa Sharaf, Douglas I. Lin, Caterina I. Colón, Zoe Fleishmann, Ericka M. Ebot, Justin Y. Newberg, Jennifer M. Mills, Priti S. Hegde, Quintin Pan, Afshin Dowlati, Garrett M. Frampton, Julien Sage, Christine M. Lovly

Supplementary Table S1: First-, second-, and third-line systemic therapy in the SCLC clinical cohort. Supplementary Table S2: Genes analyzed as part of this study. Supplementary Table S3: Prevalence of alterations in the genes analyzed. Supplementary Table S4: Prevalence of gene alterations in 81 cases with liquid biopsies. Supplementary Table S5: Chromosomal losses and gains in SCLC. Supplementary Table S6: TET2 loss of function alterations detected in SCLCs. Supplementary Table S7: Manual review of specific mutation subgroups in SCLCs. Supplementary Table S8: Patterns of gene alterations in SMARCA4 altered and wild-type tumors. Supplementary Table S9: Prevalence of gene alterations in rearrangement-positive SCLCs. Supplementary Table S10: Univariate analysis of association between gene alterations and overall surival in the clinical cohort of stage III/IV SCLC tumors. Supplementary Table S11: Patterns of tumor mutational burden based on site of biopsy. Supplementary Table 12: Summary of tumor purity and tumor mutational burden by biopsy site. Supplementary Table S13: Aneuploidy patterns based on site of biopsy. Supplementary Table S14: Comparison of gene alterations in each biopsy site against lung biopsies. Supplementary Table S15: Comparison of gene alterations in liver and brain metastases. Supplementary Table S16: Summary of PTEN alterations in brain and other biopsy sites. Supplementary Table S17: Patterns of co-occurrence and mutual exclusivity between gene alterations in the overall SCLC cohort. Supplementary Table S18: Patterns of gene alterations in TP53 and/or RB1 mutant and wild-type cohorts. Supplementary Table S19: Patterns of gene alterations in young and older patients with SCLC. Supplementary Table S20: Patterns of gene alterations in HPV positive and HPV negative tumors. Supplementary Table S21: Manual review of specific HPV+ SCLCs. Supplementary Table S22: Patterns of gene alterations in STK11 mutant and wild-type cohorts. Supplementary Table S23: Patterns of gene alterations in EGFR mutant and wild-type cohorts. Supplementary Table S24: EGFR kinase domain alterations identified in the overall SCLC cohort.


National Institutes of Health (NIH)

LUNGevity Foundation award



Small cell lung cancer (SCLC) is a recalcitrant neuroendocrine carcinoma with dismal survival outcomes. A major barrier in the field has been the relative paucity of human tumors studied. Here we provide an integrated analysis of 3,600 “real-world” SCLC cases. This large cohort allowed us to identify new recurrent alterations and genetic subtypes, including STK11-mutant tumors (1.7%) and TP53/RB1 wild-type tumors (5.5%), as well as rare cases that were human papillomavirus–positive. In our cohort, gene amplifications on 4q12 are associated with increased overall survival, whereas CCNE1 amplification is associated with decreased overall survival. We also identify more frequent alterations in the PTEN pathway in brain metastases. Finally, profiling cases of SCLC containing oncogenic drivers typically associated with NSCLC demonstrates that SCLC transformation may occur across multiple distinct molecular cohorts of NSCLC. These novel and unsuspected genetic features of SCLC may help personalize treatment approaches for this fatal form of cancer. Minimal changes in therapy and survival outcomes have occurred in SCLC for the past four decades. The identification of new genetic subtypes and novel recurrent mutations as well as an improved understanding of the mechanisms of transformation to SCLC from NSCLC may guide the development of personalized therapies for subsets of patients with SCLC.This article is highlighted in the In This Issue feature, p. 1501

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