TCGA Pheochromocytoma and Paraganglioma (PCPG, Cancer Cell 2017)

Overview

The pcpg_tcga_pub dataset is the TCGA pheochromocytoma and paraganglioma (PCPG) publication cohort, comprising multi-platform molecular profiling of 173 PCC/PGL tumors. Published in Cancer Cell (2017) by the TCGA PCPG Analysis Working Group, it represents the largest integrated genomic characterization of these rare neuroendocrine tumors. The study defines four molecular subtypes (kinase signaling, pseudohypoxia, Wnt-altered, cortical admixture), identifies CSDE1 as a novel somatically-mutated driver, and discovers recurrent fusion genes involving MAML3, BRAF, NGFR, and NF1. Head and neck paragangliomas were excluded due to insufficient post-embolization tumor tissue.

Composition

  • 173 patients with pheochromocytoma (PHC) or paraganglioma (PGNG).
  • 57% female, 43% male; mean age at diagnosis 47 years (range 19–83).
  • 11/173 (6%) had distant metastases; 16/173 (9%) had aggressive disease (distant metastases, positive regional lymph nodes, or local recurrence).
  • Plasma/urine biochemistry available for 144/173 (83%); clinical genetic testing results for 116/173 (67%).
  • Head and neck PGLs excluded (often embolized prior to surgery).
  • Geographic mix includes sporadic and hereditary cases.

Assays / panels (linked)

Papers using this cohort

  • PMID:28162975 — TCGA PCPG Analysis Working Group 2017. Multi-platform characterization of 173 PCC/PGLs; identified CSDE1 as a novel driver, discovered recurrent MAML3/BRAF/NGFR/NF1 fusions, defined four molecular subtypes, and established the Wnt-altered subtype (MAML3 fusions + CSDE1 mutations) as a marker of aggressive/metastatic disease.

Notable findings derived from this cohort

  • A driver mutation, fusion gene, or copy-number alteration was identified in 95% of PCC/PGLs PMID:28162975.
  • Pathogenic germline mutations in eight known susceptibility genes detected in 46/173 (27%): SDHB (9%), RET (6%), VHL (4%), NF1 (3%); rarer germline events in SDHD, MAX, EGLN1, TMEM127 PMID:28162975.
  • Low somatic mutation rate (mean 0.67 mutations/Mb), among the lowest across TCGA cancer types PMID:28162975.
  • Five MutSig2-significant somatic driver genes (q<0.05): HRAS, NF1, EPAS1, RET, and newly identified CSDE1 PMID:28162975.
  • Recurrent fusion genes: UBTF–MAML3 (7 tumors), TCF4–MAML3 (1 tumor), KIAA1737–NGFR, RUNDC1–BRAF, NF1–RAB11FIP4; 10 tumors total were MAML3 fusion-positive PMID:28162975.
  • Four mRNA expression subtypes: kinase signaling (NF1/RET/HRAS/TMEM127-enriched), pseudohypoxia (SDH/VHL/EPAS1-enriched), Wnt-altered (MAML3 fusions + CSDE1 mutations, associated with aggressive disease and metastasis), cortical admixture (elevated adrenocortical markers, MAX germline mutations) PMID:28162975.
  • Wnt-altered subtype MAML3 fusion-positive tumors overexpressed MAML3 2.7-fold (p<5e-6), showed expansive hypomethylation (4,229 significant probes), and activated Wnt/Hedgehog signaling (WNT4, WNT5A, GLI2) PMID:28162975.
  • Markers of poor aggressive-disease-free survival: MAML3 fusion, SDHB germline mutation, somatic SETD2 or ATRX mutation, high somatic mutation total, Wnt-altered and pseudohypoxia mRNA subtypes, hypermethylated DNA methylation subtype PMID:28162975.

Sources

  • cBioPortal study: pcpg_tcga_pub
  • Published: TCGA PCPG Analysis Working Group, Cancer Cell 2017.

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