- Gene affected:
- ASXL1: Additional sex combs like 1 gene (NM_015338.5)
- Clinical significance
- ASXL1 mutations are a prognostic biomarker that are associated with shorter overall survival time in myeloid disorders (note importance of co-mutation).
Function of gene
ASXL1 acts as an epigenetic regulator*. Although the precise mechanism of action for ASXL1 is not fully understood, is is known that ASXL1 is a chromatin binding protein that forms a scaffold for transcription activators, repressors, and related proteins. The function of ASXL1 is affected by frameshift and nonsense mutations affecting exons 11 and 12; these result in loss of ASXL1 expression which ultimately (via an intermediate pathway involving PRC2-mediated gene repression) they promote myeloid transformation and leukaemogenesis.
NGS panel gene coverage
The panel covers clinically significant mutation sites affecting exons 11 and 12 of ASXL1
Associated genetic changes:
- ASXL1 mutation is associated with concurrent mutation of RUNX1 and spliceosome mutations.
- Adverse effect may be worsened by RUNX co-occurrence.
- Mutation is inversely correlated with FLT3-ITD or NPM1 or 'DMNT3A mutation.
- GeneWiki link:
- 3. ASLX1 in AML
- 4. ASLX1 in AML