Pituitary Neuroendocrine Tumors (MSK, 2024)

Overview

Two-arm MSK cohort designed to characterize the genomic landscape of treatment-refractory and benign pituitary neuroendocrine tumors (PitNETs). A retrospective arm (n = 26) enriched for aggressive/treatment-refractory tumors (85% treatment-refractory, 38% metastatic) was profiled by MSK-IMPACT and whole-exome sequencing. A prospective arm (n = 66) captured unselected patients presenting for pituitary surgery. Data deposited in cBioPortal as ptad_msk_2024 and dbGaP (phs001783). PMID:38758238

Composition

  • Retrospective cohort: 26 patients with aggressive/treatment-refractory or higher-risk PitNETs (22/26 treatment-refractory; 10/26 metastatic).
  • Prospective cohort: 66 unselected patients undergoing pituitary surgery at MSKCC.
  • Analytic groups after stratification by radiotherapy response: 23 treatment-refractory vs. 69 benign PitNETs.
  • Cancer type: pituitary adenoma / PitNET (PTAD).
  • All tumors sequenced via MSK-IMPACT; retrospective cohort also underwent whole-exome sequencing for USP8 mutation detection. PMID:38758238

Assays / panels (linked)

  • MSK-IMPACT — primary somatic mutation and copy-number profiling.
  • Whole-exome sequencing — retrospective arm only, for USP8 mutations not covered by IMPACT.
  • FACETS v0.5.6 — allele-specific copy-number and LOH inference.
  • FISH — five patients to validate chromosomal losses.

Papers using this cohort

  • PMID:38758238 — Genome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors.

Notable findings derived from this cohort

  • Treatment-refractory PitNETs had significantly higher TMB (p = 1.3 × 10^-10) and fraction of LOH (p = 8.5 × 10^-9) compared to benign tumors. PMID:38758238
  • TP53 mutations were the most common alteration in treatment-refractory tumors (12/23 vs. 1/69 benign; p = 4.2 × 10^-8); 11/12 were clonal. PMID:38758238
  • A recurrent chromosomal LOH (rcLOH) pattern involving chromosomes 1, 2, 3, 4, 6, 10, 11, 15, 17, 18, 21, and 22 was identified in 11/14 treatment-refractory corticotroph PitNETs vs. 1/14 benign (p = 1.7 × 10^-4). PMID:38758238
  • A binary LOH threshold of 0.11 achieved AUC = 0.87, accuracy = 0.88 (sensitivity 0.83, specificity 0.90) for predicting treatment-refractory behavior. PMID:38758238
  • Five treatment-refractory corticotroph tumors harbored mismatch repair mutations (MSH2, MSH6, MLH1); 3/4 pre-treatment tumors were MSI-high. PMID:38758238
  • ATRX, DAXX, TERT, and TSC2 mutations were unique to treatment-refractory corticotroph tumors. PMID:38758238

Sources

  • cBioPortal study ptad_msk_2024. PMID:38758238
  • dbGaP accession phs001783.

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