Small Cell Lung Cancer (CLCGP, Nature Genetics 2012)

Overview

99 surgically resected SCLC specimens collected by the Clinical Lung Cancer Genome Project (CLCGP) consortium and analysed by multi-platform genomic profiling. Published in Nature Genetics 2012. The study established universal biallelic inactivation of TP53 and RB1, identified recurrent histone-modifier mutations, and nominated FGFR1 amplification as a potential therapeutic target. PMID:22941188

Composition

  • 99 surgically resected SCLC specimens total.
  • Exome sequencing: 27 tumours + 2 cell lines (n = 29).
  • Whole-genome sequencing: 2 tumours.
  • Transcriptome sequencing (RNA-seq): 15 tumours.
  • SNP array (Affymetrix SNP 6.0): 63 tumours.
  • Mouse model validation: 20 SCLC tumours from p53/Rb1 conditional knockout mice.
  • Validation cohort: 26 additional tumours + 34–45 cell lines (gene-specific).
  • Cancer type: SCLC. PMID:22941188

Assays / panels (linked)

Papers using this cohort

  • PMID:22941188 — primary characterisation study (Peifer et al., Nature Genetics 2012)

Notable findings derived from this cohort

  • Universal biallelic inactivation of TP53 and RB1 in all 29 sequenced cases; CNLOH enrichment confirms these as early clonal events. PMID:22941188
  • Mutation rate of 7.4 ± 1 protein-changing mutations per million base pairs; elevated C:G>A:T transversions consistent with tobacco carcinogen exposure. PMID:22941188
  • CREBBP/EP300 mutations (HAT domain) in 18%; mutually exclusive; functional validation showed reduced H3K18 acetylation. PMID:22941188
  • FGFR1 focal amplification in 6% of cases, validated by FISH in 51 independent tumours (3/51, 6%). PMID:22941188
  • MYCL amplification in 8%, MYCN in 6%, MYC in 1/63; all mutually exclusive (total 16%). PMID:22941188
  • SLIT2 mutated in 10% in extended cohort; PTEN mutations in 3/29 cases. PMID:22941188

Sources

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