Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling

Head Neck. 2019 Jun;41(6):1928-1934. doi: 10.1002/hed.25634. Epub 2019 Feb 13.

Abstract

Introduction: Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Those ATC with genomic alterations (GAs) in TSC2, ALK, and BRAF may respond to targeted therapies.

Methods: Comprehensive genomic profiling on 90 ATC specimens identified base substitutions, short insertions and deletions, amplifications, copy number alterations, and genomic rearrangements in up to 315 cancer-related genes and 28 genes commonly rearranged in cancer.

Results: Median patient age was 65 (range, 33-86) years, 50 patients were male. There was a mean of 4.2 GA per case, range 1-11. The most common GA were TP53 (66%), BRAF (34%), TERT (32%), CDKN2A (32%), and NRAS (26%). BRAF V600E and NRAS/HRAS/KRAS alteration were mutually exclusive. BRAF, CDKN2A, PIK3CA, and JAK2 were more frequent in patients >70 years of age; while myc, PTEN, and NRAS were more common in those ≤50 years.

Conclusion: ATC shows many GA with potential therapeutic significance and suggesting different molecular pathways can lead to ATC.

Keywords: anaplastic; neoplasms; thyroid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Prevalence
  • Thyroid Carcinoma, Anaplastic / diagnosis*
  • Thyroid Carcinoma, Anaplastic / genetics*
  • Thyroid Carcinoma, Anaplastic / therapy
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / therapy