ASXL1 Gene Sequencing
Definition
Frameshift/nonsense mutations in exon 12 (the penultimate exon) of the ASXL1 gene truncate the conserved C-terminal PHD domain and disrupt protein function; ASXL1 plays a role in chromatin regulation. Its frequency varies by myeloid disease type: about 45% in CMML, 11 to 21% in MDS, and an average of about 12 to 15% in AML; it is associated with older age, a prior history of MDS, and trisomy 8. Prognostically, an ASXL1 mutation is an independent marker of poor prognosis; overall survival and event-free survival are significantly shorter in mutated patients. In t(8;21)/RUNX1-RUNX1T1 specific AML, a similar chromatin-regulator family gene, ASXL2, has also been described with mutation enrichment specific to this translocation.
Gene/Region Examined
ASXL1 Exon 12
Method
DNA analysis
Accepted Sample Types
Blood (EDTA), Bone marrow (EDTA)
Description
AML prognosis.
Inheritance
The truncating mutations found in exon 12/13 in myeloid malignancies are somatic (acquired driver mutations). Germline de novo truncating mutations in the same region cause Bohring-Opitz syndrome, a rare developmental disorder (no reported association with AML); rare familial cases of germline ASXL1 mutation (father-son AML) have also been described.