Detection of Recurrent Mutations by Pooled Targeted Next-Generation Sequencing in MDS Patients Prior to Treatment with Hypomethylating Agents or Stem Cell Transplantation | Aplastic Anemia and MDS International Foundation

Detection of Recurrent Mutations by Pooled Targeted Next-Generation Sequencing in MDS Patients Prior to Treatment with Hypomethylating Agents or Stem Cell Transplantation

Original Publication Date: 
Tuesday, January 1, 2013

Note: This review is based upon a presentation at the 2012 American Society of Hematology (ASH) Annual Meeting, December 7-10 in Atlanta, Georgia.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report.

Abstract #311

Rafael Bejar, MD, PhD1, Kristen E. Stevenson, MS2, Petar Stojanov3, J. Eric Zaneveld4, Michal Bar-Natan5, Bennett Caughey6, Hui Wang, Ph.D.7, Guillermo Garcia-Manero, MD8, Hagop M. Kantarjian, MD9, Corey Cutler, MD, MPH, FRCPC10, Jerome Ritz, MD11, Kristian Cibulskis3, Gad Getz, PhD12, David P. Steensma, MD13, Richard M. Stone, MD14, Rui Chen, Ph.D.15, Donna S. Neuberg, ScD16 and Benjamin L. Ebert, MD, PhD17 

Myelodysplastic syndrome (MDS) affects different patients in different ways. Researchers are discovering some genetic mutations, or changes, that explain some of these differences.

Researchers recently used next-generation sequencing to identify genetic mutations in DNA from two groups of MDS patients before their MDS treatment. The first group (Cohort 1) consisted of 200 patients who were treated with Vidaza® (azacitidine), Dacogen® (decitabine), or both azacitidine and decitabine. The 76 patients in Cohort 2 underwent a stem cell transplant.

The researchers focused on 74 genes, including all genes known to be mutated in people with MDS. They excluded any genetic mutations found in at least 1% of the general population.

Key Findings:

  • The most common mutations in Cohort 1 were in the ASXL1 (39% of patients), SF3B1 (24%), TET2 (23%), RUNX1 (19%), SRSF2 (18%), and DNMT3A (15%) genes.
  • The most common mutations in Cohort 2 were in the ASXL1 (25% of patients), TP53 (22%), DNMT3A (17%), and RUNX1 (14%) genes.  
  • In Cohort 2, 37% of patients had a mutation in a splicing factor gene (SF3B1, U2AF1, SRSF2, or ZRSR2). These genes help cells splice together certain DNA sequences as part of the protein-formation process.
  • A larger proportion of patients in Cohort 2 than Cohort 1 had a genetic mutation associated with a poor prognosis (especially TP53). Also, fewer Cohort 2 patients had a genetic mutation associated with a neutral or favorable prognosis (such as SF3B1 and TET2).

Conclusions:

  • Next-generation sequencing can be used to identify genetic mutations associated with MDS in most MDS patients.

Information on individual genetic mutations in patients with MDS might be useful for predicting which patients will respond to certain treatments

Reviewer Bio: