Small Cell Lung Cancer (JHU, Nature Genetics 2012)

Overview

80 human SCLC samples (36 primary tumour-normal pairs, 17 matched cell lines, 4 unpaired primary tumours, and 23 unpaired cell lines) characterised by exome sequencing, whole-genome sequencing, RNA-seq, and copy-number analysis at Johns Hopkins University. Published in Nature Genetics 2012. The study identified SOX2 amplification as a major oncogenic event and discovered the recurrent RLF-MYCL fusion transcript. PMID:22941189

Composition

  • 80 human SCLC samples total: 36 primary tumour-normal pairs, 17 paired cell lines with matched lymphoblastoid lines, 4 unpaired primary tumours, 23 unpaired cell lines.
  • 56 samples assayed by Illumina HumanOmni2.5 SNP arrays for copy-number analysis.
  • 110 independent primary SCLC tumour samples used for SOX2 IHC/FISH validation.
  • Reference genome: GRCh37/hg19.
  • Cancer type: SCLC. PMID:22941189

Assays / panels (linked)

  • whole-exome-seq — 42 tumour-normal pairs (primary + cell lines)
  • whole-genome-seq — structural variant detection
  • rna-seq — fusion transcript discovery (RLF-MYCL)
  • gistic — copy-number analysis from Illumina HumanOmni2.5 SNP arrays

Papers using this cohort

  • PMID:22941189 — primary characterisation study (Rudin et al., Nature Genetics 2012)

Notable findings derived from this cohort

  • 22 significantly mutated genes identified (q ≥ 1, FDR ≤ 10%) including TP53 and RB1. PMID:22941189
  • Mean nonsynonymous mutation rate 5.5 mutations/Mb (excluding one hypermutated sample); G-to-T transversions predominant (tobacco). PMID:22941189
  • SOX2 amplification (copy number ≥ 4) in ~27% (15/56) of samples; shRNA knockdown reduced proliferation (P < 0.01). PMID:22941189
  • Recurrent RLF-MYCL fusion found in 1 primary tumour and 4 cell lines; siRNA targeting MYCL reduced proliferation in fusion-positive lines. PMID:22941189
  • Mutations in PI3K pathway (PIK3CA, AKT1-3, MTOR), SOX family, Notch/Hedgehog (NOTCH1, SMO), and chromatin-modifying genes (EP300). PMID:22941189
  • Four kinase gene fusions identified: NPEPPS-EPHA6, SKP1-CDKL3, NEK4-SFMBT1, ZAK-RAPGEF4. PMID:22941189

Sources

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