Thymic Carcinoma (THYC)

Overview

Thymic carcinoma is an aggressive thymic epithelial malignancy; in OncoTree THYC is a child of TET under THYMUS. Unlike indolent thymomas, thymic carcinomas carry high mutation burden, frequent copy-number aberrations, and recurrent mutations in TP53, CYLD, CDKN2A, BAP1, and PBRM1 — resembling aggressive epithelial cancers — with GTF2I hotspot mutation found in only 8% (3/36) of cases.

Cohorts in the corpus

Recurrent alterations

  • TP53, CYLD, CDKN2A, BAP1, and PBRM1 are recurrently mutated in thymic carcinomas; mean 43.5 somatic mutations per sample vs 18.4 in thymomas (Mann-Whitney U P=0.001) PMID:24974848.
  • GTF2I p.Leu404His present in only 8% (3/36) of thymic carcinomas; all three GTF2I-mutant thymic carcinoma patients were alive at median 27.6 months (too few for robust inference) PMID:24974848.
  • KIT mutations in ~10% of thymic carcinomas (literature context cited in paper); the three GTF2I-mutant thymic carcinomas in the cohort were KIT-positive by IHC PMID:24974848.
  • BRD4–NUTM1 fusion confirmed in TY82 thymic carcinoma cell line PMID:24974848.
  • Copy-number burden enriched relative to thymomas: arm-level gains (1q, 7p, 7q, 20p) and losses (6p, 6q, 3p, 13q) more frequent in aggressive histotypes PMID:24974848.
  • In the MSK-IMPACT pan-cancer cohort, thyroid cancer (THYC) had a TERT promoter mutation rate of 60% (3rd highest after BLCA 70% and glioma 67%); 60% of thyroid patients harbored an OncoKB-actionable alteration (2nd highest after GIST 76%). PMID:28481359

Subtypes

  • Includes squamous cell carcinoma, undifferentiated carcinoma, and NUT carcinoma (BRD4-NUT) variants.

Therapeutic landscape

  • KIT mutation (~10%) is the principal targetable lesion in thymic carcinomas; imatinib has been used in KIT-mutant cases (not directly evaluated in PMID:24974848).

Sources

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