KANSL1

Overview

KANSL1 (KAT8 Regulatory NSL Complex Subunit 1) encodes a component of the NSL histone acetyltransferase complex, which acetylates histone H4 at multiple lysines to regulate gene expression. In cancer genomics, KANSL1 is implicated as a HAT-complex subunit recurrently altered in medulloblastoma, particularly in the SHH subgroup.

Alterations observed in the corpus

  • Recurrent alteration as part of HAT-complex mutations in SHH medulloblastoma (19% of SHH cases collectively with KAT6B, CREBBP, EP300, BRPF1) PMID:28726821
  • Histone acetylase significantly mutated gene (SMG) in muscle-invasive bladder cancer (MIBC, n=412, TCGA BLCA 2017); part of the pervasive chromatin-modifier mutation cluster. PMID:28988769

Cancer types (linked)

  • SHH medulloblastoma: HAT-complex subunit altered as part of a recurrent epigenetic driver class affecting 19% of SHH tumors PMID:28726821

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • HAT-complex alterations in SHH medulloblastoma may sensitize to epigenetic therapeutic approaches, though no direct targeted therapy is established.

Open questions

  • The functional consequence of individual KANSL1 alterations vs. collective HAT-complex disruption in medulloblastoma subtype biology remains to be resolved.

Sources

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