TCGA Head and Neck Squamous Cell Carcinoma (2015)

Overview

The Cancer Genome Atlas (TCGA) multi-platform genomic characterization of 279 head and neck squamous cell carcinomas (HNSCC), published in Nature in 2015. The study profiled tumors from oral cavity (62%), larynx (26%), and oropharynx (12%) with whole-exome sequencing (mean coverage 95×), supplemented by low-pass whole-genome sequencing (n=29), RNA-seq, miRNA-seq, DNA methylation (HM450), RPPA, and SNP6.0 arrays. The cohort defines two major disease biologies based on HPV status: HPV-positive (n=36) and HPV-negative (n=243) tumors, with distinct mutational landscapes, copy-number profiles, and mRNA expression subtypes.

Composition

  • n=279 HNSCC with complete multi-platform data (drawn from a larger 500-tumour TCGA target).
  • Anatomic sites: oral cavity 172 (62%), larynx 72 (26%), oropharynx 33 (12%), plus rare hypopharynx cases.
  • Predominantly male (73%) and heavy smokers (mean 51 pack-years).
  • HPV status by RNA-seq E6/E7 mapping (threshold >1,000 reads): 36 HPV(+), 243 HPV(−). 64% of oropharyngeal tumours HPV(+) vs 6% of non-oropharyngeal tumours.
  • Cancer types: HNSC, OCSC, OPHSC, LXSC, HPHSC.

Assays / panels (linked)

Papers using this cohort

  • PMID:25631445 — TCGA Network (2015). Comprehensive genomic characterization of 279 HNSCCs; identified 11 significantly mutated genes (MutSigCV q < 0.1), HPV(+)/HPV(−) biologic dichotomy, four mRNA subtypes, and candidate therapeutic alterations in most tumors.

Notable findings derived from this cohort

  • Eleven significantly mutated genes (MutSigCV q < 0.1): TP53 72%, FAT1 23%, CDKN2A 22%, PIK3CA 21%, NOTCH1 19%, KMT2D 18%, NSD1 10%, CASP8 9%, AJUBA 6%, NFE2L2 6%, HLA-A 3%. PMID:25631445
  • TP53 mutated in 86% of HPV(−) tumors but only 1/36 HPV(+) cases; PIK3CA mutated in 56% of HPV(+) vs 34% of HPV(−), with helical-domain enrichment in HPV(+). PMID:25631445
  • Novel recurrent inactivation of TRAF3 in HPV(+) tumors (deletions 14%, truncating mutations 8%), representing the first link between TRAF3 loss and HPV-associated carcinoma. PMID:25631445
  • NSD1 inactivated in 33 tumors (10%) by mutations or focal homozygous deletions; associated with DNA hypomethylation. PMID:25631445
  • Four mRNA expression subtypes confirmed (atypical 24%, mesenchymal 27%, basal 31%, classical 18%), each with distinct co-occurring genomic features; classical subtype resembles lung squamous cell carcinoma (LUSC) with tobacco and oxidative-stress signatures. PMID:25631445
  • Favourable outcomes in HPV(+) and HPV(−)/TP53-wild-type tumors vs poor outcomes in TP53-mutant and 11q13/CCND1-amplified tumors; co-amplification of 11q13 (CCND1, FADD, CTTN) and 11q22 (BIRC2, YAP1) in 31% of HPV(−) tumors. PMID:25631445
  • Oral-cavity CNA-low “M class” subset defined by activating HRAS + inactivating CASP8 + wild-type TP53; favourable clinical outcome. PMID:25631445

Sources

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