ArticleNature communications2021
Multi-region exome sequencing reveals the intratumoral heterogeneity of surgically resected small cell lung cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer-A Systematic Review of the Current Status.International journal of molecular sciences · 2024Pooled it
- RESILIENT Part 2: A Randomized, Open-Label Phase III Study of Liposomal Irinotecan Versus Topotecan in Adults With Relapsed Small Cell Lung Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer.Nature communications · 2026Article
- A Hallmark-Integrated, Agent-Based Framework for Intratumor Heterogeneity in Melanoma Evolution.Bulletin of mathematical biology · 2026Article
- Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer.Cell reports. Medicine · 2026Article
- Oocyte-inspired universal whole-cell vaccines against tumor heterogeneity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Evaluating the prognostic value of mutational signatures in small-cell lung cancer through reference-based signature assignment and continuous activity analysis.Frontiers in genetics · 2026Article
- Decoding intertumoral heterogeneity in multifocal ground-glass nodule lung cancers: Clonal evolutionary insight for precision management.JTCVS open · 2025Article
- Comprehensive Genomic Profiling of Small-Cell Lung Cancer Reveals Frequent Potentially Targetable Alterations.International journal of molecular sciences · 2025Article
- Small cell lung cancer: relationship with HLA-I alleles and gene mutation.Journal of cardiothoracic surgery · 2025Article
- Genome-level selection in tumors as a universal marker of resistance to therapy.Nature communications · 2025Article
- Genomic alterations and transcriptional phenotypes in circulating free DNA and matched metastatic tumor.Genome medicine · 2025Article
- Tumor Heterogeneity and Plasticity in Small Cell Lung Cancer.Lung Cancer (Auckland, N.Z.) · 2025Review
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- Tumor mutation burden andTranslational lung cancer research · 2024Article
- Molecular landscape and multi-omic measurements of heterogeneity in fetal adenocarcinoma of the lung.NPJ precision oncology · 2024Article
- Genomic alterations and transcriptional phenotypes in circulating tumor DNA and matched metastatic tumor.bioRxiv : the preprint server for biology · 2024Article
- HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.Genome biology · 2024Article
- Comparison of clinicopathological features and survival analysis between esophageal neuroendocrine carcinoma and esophageal squamous cell carcinoma based on the SEER database, alongside nomogram analysis for esophageal neuroendocrine carcinoma.Journal of gastrointestinal oncology · 2023Article
- HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
28 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small cell lung cancer (SCLC) is a highly malignant tumor which is eventually refractory to any treatment. Intratumoral heterogeneity (ITH) may contribute to treatment failure. However, the extent of ITH in SCLC is still largely unknown. Here, we subject 120 tumor samples from 40 stage I-III SCLC patients to multi-regional whole-exome sequencing. The most common mutant genes are TP53 (88%) and RB1 (72%). We observe a medium level of mutational heterogeneity (0.30, range 0.0~0.98) and tumor mutational burden (TMB, 10.2 mutations/Mb, range 1.1~51.7). Our SCLC samples also exhibit somatic copy number variation (CNV) across all patients, with an average CNV ITH of 0.49 (range 0.02~0.99). In terms of mutation distribution, ITH, TMB, mutation clusters, and gene signatures, patients with combined SCLC behave roughly the same way as patients with pure SCLC. This condition also exists in smoking patients and patients with EGFR mutations. A higher TMB per cluster is associated with better disease-free survival while single-nucleotide variant ITH is linked to worse overall survival, and therefore these features may be used as prognostic biomarkers for SCLC. Together, these findings demonstrate the intratumoral genetic heterogeneity of surgically resected SCLC and provide insights into resistance to treatment.
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