Whole Exome Sequencing Identifies Cohesin Component STAG1 Mutation in de novo Acute Myeloid Leukemia (FAB M2): A Pilot Study with Cytogenetics, Clinical and Prognostic Implications.

The clinical implications of cohesin gene complex mutation in acute myeloid leukemia (AML) are not well characterized. In the present study, a cohort of 152 de novo unselected adult AML patients underwent conventional and molecular cytogenetic analysis for chromosomal aberrations. Further, we examined the frequency and clinical implications of mutations in cohesin gene complex STAG1, STAG2, RAD21, SMC1, and SMC3 using whole exome sequencing as a pilot study in 10 de novo patients with AML-FAB M2. Among the 10 cases, we identified a functionally heterozygous mutation in exon16 of STAG1 in one patient (10%), however no mutation was observed in STAG2, RAD21, SMC1, and SMC3. Sanger sequencing analysis for exon 16 of STAG1 in the remaining 142 AML cases did not reveal any further mutations, which underlined the observation that mutations took place throughout the cohesin gene complex without presence of a mutational hot spot region. The present study identified a positive correlation between serum bilirubin, LDH, and hematological parameters such as Hb, WBC, and platelet count with STAG1 mutation. Our data suggest that the cohesin complex may represent an attractive therapeutic target for future preclinical and clinical studies. However, more studies with a larger number of patients should be performed prospectively to determine the pathogenic involvement of STAG 1 mutation in AML patients.