YEATS4

Overview

YEATS4 (also known as GAS41) is a chromatin reader and transcriptional regulator that is recurrently co-amplified with MDM2 and CDK4 on chromosome 12q in dedifferentiated liposarcoma. Functional studies suggest it cooperates with MDM2 to repress p53 network activity, making it a candidate therapeutic target in DDLS.

Alterations observed in the corpus

  • Co-amplified with MDM2 on chromosome 12q in ~90% of dedifferentiated liposarcomas (DDLS); YEATS4 was upregulated in amplified vs copy-neutral tumors and in tumors vs normal adipose tissue; YEATS4 knockdown phenocopied MDM2 knockdown in anti-proliferative effect in a 385-gene shRNA screen across three DDLS cell lines (LPS141, DDLS8817, FU-DDLS-1); proposed to cooperatively repress the p53 network alongside MDM2, providing rationale for MDM2 antagonists (nutlin-3a) in DDLS (sarc_mskcc, n=207) PMID:20601955.

Cancer types (linked)

  • DDLS — co-amplified on 12q with MDM2; functional dependency confirmed by shRNA; upregulated in amplified vs copy-neutral tumors PMID:20601955.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • YEATS4 knockdown anti-proliferative in DDLS; co-amplification with MDM2 supports evaluation of p53–MDM2 interaction antagonists (nutlin-3a) as a therapeutic strategy PMID:20601955.

Open questions

  • Mechanistic basis for YEATS4-mediated p53 repression (chromatin reading vs. direct transcriptional regulation) was not established in this study; further functional characterization needed.

Sources

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