Cutaneous Squamous Cell Carcinoma — HGSC/BCM 2014

Overview

Whole-exome sequencing of 39 aggressive cutaneous squamous cell carcinomas (cSCCs) of the head and neck region, generated by Pickering et al. (2014) at MD Anderson Cancer Center with sequencing performed at the Human Genome Sequencing Center, Baylor College of Medicine. All cases were clinically aggressive (regional/distant metastasis or features linked to mortality). Variant calling via the HGSC Mercury pipeline.

Composition

  • Cancer type: CSCC (cutaneous squamous cell carcinoma).
  • Samples: 39 patients; snap-frozen tumor paired with matched normal blood.
  • Aggression criteria: 38.5% recurrent, 25.6% persistent, 35.9% previously untreated; 71.8% invaded beyond subcutaneous space; 48.7% perineural invasion; 43.6% poorly differentiated; 100% Clark level ≥4.
  • Metastatic-site samples: 7.

Assays / panels (linked)

  • whole-exome-seq — Illumina HiSeq 2000; HGSC VCRome 2.1 42 Mb capture; mean 115× coverage.
  • mutsig CV v1.4 driver discovery; absolute for copy-number / purity/ploidy estimation; IntOGen v2.3.0 and two custom inactivation-bias algorithms.

Papers using this cohort

  • PMID:25303977 — Pickering et al. (2014), Clinical Cancer Research. Mutational landscape of aggressive cutaneous squamous cell carcinoma.

Notable findings derived from this cohort

  • Extreme UV-driven mutation burden: median 61.2 mutations/Mb (>4× the melanoma rate); 75% C>T transitions typical of UV signature PMID:25303977.
  • 23 candidate driver genes identified; TP53 (94.9%), NOTCH1 (59%), NOTCH2 (51.3%), CDKN2A (43.6%), FAT1 (43.6%), KMT2D (69.2%), KMT2C (38.5%), CASP8 (23.1%), AJUBA (23.1%), HRAS (20.5%) among the most frequent PMID:25303977.
  • KMT2C mutation strongly associates with bone invasion (53% vs 10%, P=0.008) and shorter recurrence-free survival (HR 5.16; P=0.003) PMID:25303977.
  • NOTCH2 emerges as a novel candidate tumor suppressor; mutation associated with perineural invasion (70% mutant vs 33% wild-type, P=0.04) PMID:25303977.
  • Four “nasal” tumors lacked the UV signature and resembled HPV-negative HNSC, suggesting mucosal rather than cutaneous origin PMID:25303977.

Sources

  • cBioPortal study: cscc_hgsc_bcm_2014.

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