Renal Non-Clear Cell Carcinoma (NCCRCC)
Overview
Renal Non-Clear Cell Carcinoma (NCCRCC) is an OncoTree grouping node under Renal Cell Carcinoma (RCC) that encompasses all RCC subtypes lacking clear-cell histology. Its OncoTree children include Papillary Renal Cell Carcinoma (PRCC), Chromophobe Renal Cell Carcinoma (CHRCC), Translocation-Associated Renal Cell Carcinoma (TRCC), and Unclassified Renal Cell Carcinoma (URCC). High-grade primary tumors that cannot be assigned to any established subtype after rigorous pathologic review are classified as URCC; URCC comprises ~4–5% of all RCC PMID:27713405.
Cohorts in the corpus
- urcc_mskcc_2016 — 62 high-grade primary unclassified RCCs (URCC subtype) from MSKCC; the cohort explicitly excluded MiTF-family translocation tumors (TFE3/TFEB IHC/FISH negative), confirming their NCCRCC classification PMID:27713405.
Recurrent alterations
Alterations vary by subtype; see individual subtype pages. Cross-NCCRCC observations:
- NF2 — recurrent in URCC (18%); also previously reported in small numbers of pRCC and collecting-duct RCC PMID:27713405.
- SETD2 — recurrent in both PRCC and URCC (18% overall in URCC, 44% in NF2-loss URCC) PMID:27713405.
- mTOR pathway (MTOR, TSC1, TSC2, PTEN) — hyperactivating mutations define 21% of URCC and 23% of CHRCC, making mTOR inhibition a cross-NCCRCC candidate strategy PMID:27713405.
- FH — FH-deficient subset in URCC (6%); germline FH mutations underlie HLRCC PMID:27713405.
- ALK fusions — TPM3–ALK fusion in 1 URCC case; TFE3/TFEB fusions define TRCC PMID:27713405.
Subtypes
- Papillary Renal Cell Carcinoma (PRCC)
- Chromophobe Renal Cell Carcinoma (CHRCC)
- Translocation-Associated Renal Cell Carcinoma (TRCC)
- Unclassified Renal Cell Carcinoma (URCC) — high-grade tumors not assignable to established subtypes; ~4–5% of all RCC; four molecularly distinct subsets defined PMID:27713405.
Therapeutic landscape
- mTOR-pathway alterations across multiple NCCRCC subtypes (URCC 21%, CHRCC 23%) support subset-stratified mTOR-inhibitor trials PMID:27713405.
- MET-targeted therapy is supported in PRCC (MET mutations 15%, chr7/MET amplification ~70%).
- NF2-loss URCC: candidate for YAP-pathway inhibitors and WEE1 synthetic-lethality (concurrent SETD2 mutation) PMID:27713405.
Sources
- PMID:27713405 — Chen et al., molecular characterization of 62 MSKCC high-grade uRCCs; contextualizes URCC within NCCRCC and provides cross-subtype molecular comparisons.
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