CSMD1

Overview

CSMD1 (CUB and Sushi Multiple Domains 1) encodes a large transmembrane protein involved in complement regulation and is located at 8p23.2, a region frequently deleted across multiple cancer types. CSMD1 has been proposed as a tumor suppressor gene and is recurrently altered in melanoma and other solid tumors.

Alterations observed in the corpus

  • Recurrently altered in melanoma; identified in a WGS study of 25 melanoma tumors examining the mutational landscape beyond the known BRAF/NRAS drivers PMID:22622578
  • Focal deletion on 8p in OSCC; candidate tumor suppressor PMID:23619168
  • Missense c.G10337A (p.G3446E) yields neoepitope GLEREGFTF that drove a polyfunctional T-cell response in melanoma patient CR0095 treated with CTLA-4 blockade; the peptide shares 80% homology with a known Burkholderia pseudomallei antigen (IEDB ID 1027043) PMID:25409260
  • CSMD1 altered in one metastasis-private non-synonymous variant in patient 99-091 in multi-metastasis mCRPC autopsy study; one of only two genes (with NCOR2) altered at >5% frequency in prad_tcga or prad_su2c_2015, suggesting the private mutation is likely not a driver PMID:26928463

Cancer types (linked)

  • MEL (melanoma): Recurrent alteration in the BRAF/NRAS-dominant mutational landscape of melanoma; specific mutation frequency not detailed but noted as a recurrently altered gene in the cohort PMID:22622578

Co-occurrence and mutual exclusivity

  • No specific co-occurrence or mutual exclusivity patterns reported in the current corpus.

Therapeutic relevance

  • No approved agents directly target CSMD1; its putative tumor suppressor role suggests that loss-of-function events may contribute to melanoma progression independently of BRAF/NRAS alterations.

Open questions

  • The mechanistic basis of CSMD1 as a tumor suppressor in melanoma (complement regulation vs. other signaling roles) is not established.
  • Whether CSMD1 loss defines a subset of melanomas with distinct biological behavior requires larger cohort validation.

Sources

This page was processed by entity-page-writer on 2026-05-06. - PMID:23619168

This page was processed by wiki-cli on 2026-05-09. - PMID:25409260

This page was processed by wiki-cli on 2026-05-14. - PMID:26928463

This page was processed by entity-page-writer on 2026-05-15.