Bejar R, Stevenson KE, Caughey B et al.
University of California, San Diego, CA, USA.
J Clin Oncol 2014;32:2691–8.
Rob Sellar’s review: Although somatic mutations are common in patients with myelodysplastic syndrome (MDS), they are not currently incorporated into routine clinical care or prognostic scoring systems. Nor is information from molecular genetics used to predict outcome for patients with MDS following allogeneic hematopoietic stem cell transplant (HSCT). Even when using well-matched donors, the 5-year overall survival (OS) rate following HSCT for MDS is only 40%, and better risk stratification may aid the decisions of who should receive a transplant and when.
This study identified 125 patients with MDS undergoing a first HSCT at the Dana–Farber Cancer Institute (Boston, MA, USA) from 2004 to 2009. After exclusion of patients with no pre-transplant material for sequencing, or for whom sequencing could not be completed, 87 patients remained. Massively parallel sequencing was performed on bone marrow mononuclear cells or peripheral blood collected prior to HSCT to assess for coding mutations in 40 genes recurrently mutated in MDS. Mutations were identified in 92% of patients, most commonly additional sex combs-like 1 (ASXL1; 29%), tumor protein p53 (TP53; 21%), and DNA methyltransferase 3α (DNMT3A; 18%). Mutations of TP53 were associated with complex karyotypes and limited numbers of mutations in other genes.