Recurrent and Metastatic Head & Neck Cancer (MSK, JAMA Oncol 2016)

Overview

Morris et al. assembled this cohort of 151 patients with advanced, treatment-resistant head and neck tumors who underwent clinical-grade genomic profiling at Memorial Sloan Kettering Cancer Center between January 2014 and July 2015, under IRB protocol NCT01775072. All samples were sequenced with the CLIA-approved MSK-IMPACT 410-gene panel, enabling genome-wide copy number analysis and paired matched normal sequencing. The study represents the first large clinical-grade molecular landscape of recurrent and metastatic head and neck cancers and is publicly available on cBioPortal.

Composition

  • N = 151 patients (95 men, 56 women; mean age 61.8 years, range 17–100).
  • Disease distribution: 53 HNSC, 56 salivary carcinomas (36 ACYC plus 20 other salivary types), 27 cutaneous carcinomas (21 CSCC, 4 BCC, 2 skin adnexal), 8 NPC, 3 HNNE, 2 odontogenic carcinomas, 2 olfactory neuroblastomas (ONBL).
  • Site distribution: 66 patients with locoregional recurrence, 106 with distant metastases, 6 with locally advanced surgically unresectable tumors.
  • Enrollment: January 2014 – July 2015 (224 enrolled total; 151 with ≥6-month follow-up).
  • Reference genome: hg19.

Assays / panels (linked)

  • IMPACT410 — MSK-IMPACT targeted NGS of 410 cancer-relevant genes; median coverage 600× (range 82×–1165×); CLIA-approved; with matched normal DNA.
  • FACETS — allele-specific copy number and clonality analysis.
  • mutational-signatures — APOBEC, tobacco, and UV-light signature decomposition.

Papers using this cohort

  • PMID:27442865 — Morris et al., “The Molecular Landscape of Recurrent and Metastatic Head and Neck Cancers: Insights From a Precision Oncology Sequencing Platform,” JAMA Oncology 2017. (Defining study for this cohort.)

Notable findings derived from this cohort

  • NGS guided therapy in 21/151 patients (14%) overall and 13/53 (25%) of HNSC patients; 28/135 (21%) harbored potentially actionable alterations. PMID:27442865
  • TERT promoter mutations identified in 53% of HPV-negative HNSC, 52% of CSCC, 75% of BCC, and 14% of ACYC — the first report of TERT promoter mutations in salivary cancers; zero in HPV-positive HNSC. PMID:27442865
  • NOTCH1 activating mutations or amplifications enriched in recurrent/metastatic ACYC (8/36, 22.2%; OR 8.3 vs primary ACYC; P=.005), with recurrent truncating events at serine 2467 nominating γ-secretase inhibitors. PMID:27442865
  • 43% of advanced HPV-positive HNSC tumors acquired an “HPV-negative-like” genotype enriched for TP53 mutation, whole-genome duplication, and 3p deletion; these tumors trended toward worse survival (HR 2.3; P=.19). PMID:27442865
  • ETV6-NTRK3 fusions reclassified 2 acinic cell carcinomas as MASC; both patients had major or near-complete responses on a TRK inhibitor basket trial. PMID:27442865
  • Mismatch repair gene mutations (MLH1 truncating, MSH2/MSH6/POLD1 missense) in 4 tumors associated with markedly elevated mutation counts (17.3 vs 4.5; P<.001). PMID:27442865

Sources

  • cBioPortal study ID: hnc_mskcc_2016
  • DOI: 10.1001/jamaoncol.2016.1790
  • IRB protocol: NCT01775072
  • Reference genome: hg19

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