Advanced Thyroid Carcinoma MSKCC 2016 (Landa et al.)

Overview

Patient-derived cohort of 117 advanced thyroid tumors — 84 poorly differentiated thyroid carcinomas (PDTC) and 33 anaplastic thyroid carcinomas (ATC) — collected at MSKCC and profiled by deep targeted sequencing (MSK-IMPACT 341-gene panel), array CGH, and transcriptomics. The defining study characterizing the genomic landscape of advanced thyroid cancers and their relationship to papillary thyroid carcinoma (PTC). Data deposited in cBioPortal under studyId thyroid_mskcc_2016. PMID:26878173

Composition

  • 117 patient-derived tumors: 84 PDTC and 33 ATC.
  • Median age: 58 years (PDTC), 66 years (ATC); female:male 1.5:1 (PDTC) and 1.2:1 (ATC).
  • 92/117 primary tumors; 25/117 nodal or distant metastases.
  • Paired normal tissue available for 106/117 (78 PDTC, 28 ATC).
  • Sample preservation: 80 FFPE / 37 fresh-frozen.
  • Transcriptomics and CNAs from 37 fresh-frozen tumors (17 PDTC + 20 ATC): Affymetrix U133 Plus 2.0 expression array and Agilent SurePrint G3 1×1M array-CGH; expression data at GEO accession GSE76039.
  • Mean sequencing depth: 584× tumor / 236× normal (739× for ATCs due to low purity from macrophage infiltration). PMID:26878173

Assays / panels (linked)

Papers using this cohort

  • PMID:26878173 — Landa et al., J Clin Invest 2016: primary discovery study defining the genomic landscape of PDTC and ATC; used thca_tcga_pub as reference comparator.

Notable findings derived from this cohort

  • Stepwise mutation-burden increase: median mutations ATC 6 > PDTC 2 > PTC 1 (each pairwise P < 1×10⁻⁴); higher burden in PDTC tracked with older age, larger tumors, distant metastasis, and worse survival PMID:26878173.
  • BRAF V600E in 33% PDTC and 45% ATC; RAS mutations in 28% PDTC and 24% ATC; mutually exclusive with BRAF and gene fusions PMID:26878173.
  • TERT promoter mutations show stepwise enrichment: 9% PTC → 40% PDTC → 73% ATC; TERT-mutant ATC patients had markedly shorter survival (median 147 vs 732 days, P = 0.03) PMID:26878173.
  • EIF1AX mutated in ~10% of advanced thyroid cancers with near-perfect co-occurrence with RAS (OR 58.3, P < 0.001); thyroid-specific p.A113splice mutation PMID:26878173.
  • TP53 mutated in 73% ATC vs 8% PDTC (P < 1×10⁻⁴) — a defining dichotomy between the two entities PMID:26878173.
  • SWI/SNF complex mutations in 36% ATC vs 6% PDTC (P = 1×10⁻⁴); histone methyltransferase mutations in 24% ATC vs 7% PDTC — first systematic characterization of chromatin-modifier disruption in advanced thyroid cancer PMID:26878173.
  • Gene fusions present in 14% of PDTC (RET/PTC, PAX8-PPARG, ALK fusions) and absent in ATC; novel NUTM1-BRD4 fusion in one ATC PMID:26878173.
  • BRAF-RAS score (BRS) showed ATCs are uniformly BRAF-like irrespective of driver, consistent with stepwise oncogenesis from differentiated precursors PMID:26878173.

Sources

  • cBioPortal study: thyroid_mskcc_2016
  • Expression data: GEO accession GSE76039
  • PMID:26878173 — Landa I et al., “Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.” J Clin Invest 2016.

This page was processed by crosslinker on 2026-05-14.