ZEB2

Overview

ZEB2 (Zinc Finger E-Box Binding Homeobox 2, also known as SIP1/ZFHX1B) encodes a transcriptional repressor that drives epithelial-to-mesenchymal transition (EMT) and plays roles in haematopoietic cell differentiation. In cancer, ZEB2 acts both as an oncogene (supporting invasion and metastasis) and as a tumour-suppressor context-dependently. In haematologic malignancies it has been identified as a recurrently mutated transcriptional regulator.

Alterations observed in the corpus

  • ZEB2 transcriptional-regulator mutations enriched in the DUX4/ERG B-ALL subtype (7.4% of cases) relative to 209 other B-ALL and 16 T-ALL comparator cases; part of the 21% of DUX4/ERG ALL cases with recurrent transcriptional-regulator mutations including MYC, MYCBP2, and MGA, in a cohort of 1,913 B-progenitor ALL patients. PMID:27776115

Cancer types (linked)

  • B-lymphoblastic leukemia (BLL): ZEB2 mutations identified as recurrent transcriptional-regulator alterations in the DUX4/ERG subtype (7.4% of 141 subtype cases, ~1% of 1,913 total B-ALL). PMID:27776115

Co-occurrence and mutual exclusivity

  • In the DUX4/ERG B-ALL subtype, ZEB2 mutations co-occur with other transcriptional-regulator mutations (MYC, MYCBP2, MGA), IKZF1 alterations (36.7%), Ras-pathway mutations (35.2%), and epigenetic-modifier mutations (56.3% of cases). PMID:27776115

Therapeutic relevance

  • No targeted therapy identified for ZEB2-mutant leukemia. DUX4/ERG ALL is associated with a favourable prognosis overall, irrespective of co-occurring IKZF1 deletions. PMID:27776115

Open questions

  • Whether ZEB2 mutations in DUX4/ERG ALL are functional drivers or passenger events has not been established by functional studies.

Sources

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