Molecular Evaluation of SF3B1 Mutations in Cytopenic Patients
Bella Goyal, Eric J Duncavage. Washington University School of Medicine, St. Louis, MO
Background: Splicesosomal genes, such as SF3B1 and U2AF1, have been recently implicated in the pathogenesis of myelodysplastic syndromes (MDS). SF3B1 mutations occur most frequently in association with ringed sideroblasts and are present in up to 50% of refectory anemias with ringed sideroblasts. SF3B1 mutations occur most commonly in exon 15. We aimed to investigate the diagnostic utility of SF3B1 testing in cytopenic patients clinically suspected of having MDS.
Design: We identified 48 newly diagnosed cytopenic patients between 2006 and 2007 who had bone marrow (BM) biopsies to evaluate for MDS. Cytogenetic findings, peripheral counts, International Prognostic Scoring System (IPSS-R), and subsequent follow up were available. Bone marrow biopsies were reviewed and 4 to 6 (1 mm) punch biopsies were taken from the paraffin blocks. DNA was then extracted and PCR amplified using primers specific for SF3B1 exon 15. Amplification was confirmed by agarose gel electrophoresis. PCR products were then bi-directionally Sanger sequenced, and the resulting sequencing traces analyzed for variants.
Results: The patient population included 32 men and 16 women with a mean age of 62 years (range = 21-94 years). At biopsy, 8 patients had an IPSS-R score of 1.0; 7 patients had an IPSS-R score of 1.5; 7 patients had an IPSS-R score of 2.0; 6 patients had a IPSS-R score of 2.5; 7 patients had a IPSS-R score of 3.0; 7 patients had a IPSS-R score of 3.5; and 6 patients had a IPSS-R score of >4.0. Of the 48 patients, 5 patients (10%) had ringed sideroblasts. Of the 48 patients, 18 patients were diagnosed with MDS by morphology, and 6 had characteristic cytogenetic findings alone. 45 of 48 BM biopsy cores were successfully PCR amplified and sequenced. 1 of 45 (2%) BM biopsies (a case with mild dyserythropoiesis, absent storage iron, and normal cytogenetics) harbored an SF3B1 mutation. The patient subsequently was diagnosed with Hodgkin Lymphoma and died shortly after bone marrow biopsy.
Conclusions: Given the relatively low mutation rate of SF3B1 in cytopenic patients, molecular testing does not appear to be a useful adjunct to standard cytogenetics and morphology in MDS evaluation. However, a panel based approach to MDS molecular testing including other frequently mutated MDS-related genes such as SF3B1, TET2, U2AF1, and ASXL1 may prove more useful.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 211, Monday Morning