IBCL-327: Genetic Instability (MSI, EMAST) in Patients with Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

Context: Genetic instability is one of the characteristic features of tumor cells and is associated with tumor progression and transformation. An integral measure of genetic instability could be assessed through STR (short tandem repeats) analysis in terms of MSI (microsatellite instability) and EMAST (elevated microsatellite alteration at selected tetranucleotides). MSI and EMAST occur as a result of DNA repair complex malfunction in tumor cells. The study presents MSI and EMAST data in patients with non-Hodgkin B-cell lymphomas: follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Objective: To determine the frequency of MSI and EMAST as predictors of the clinical course of the disease at the early stages of diagnosis in patients with FL and DLBCL. Design: FL patients (n=7) and DLBCL patients (n=5) who followed up at the National Research Center for Hematology were included in the study after receiving their informed consent. DNA samples from tumor and control DNA samples from healthy somatic cells of the same patient were isolated according to a standard protocol. Genetic instability was assessed by multiplex PCR of STR loci with COrDIS Plus and COrDIS MSI kits (Gordiz Ltd, Russia). The fragment analysis was performed on an ABI3130 Genetic Analyzer. Results: The observed frequency of MSI and EMAST in FL was 15% (1/7) and 28% (2/7); in DLBCL, 0% (0/5) and 20% (1/5), respectively. STR profiles also revealed allelic imbalance due to loss of heterozygosity (LOH) with a high incidence: 71% (5/7) and 60% (3/5) in FL and DLBCL, respectively. LOH is an independent form of genetic instability and probably associated with recombination complex disruption in tumor cells. LOH reflects the loss of a significant amount of genetic material from a single chromosome via deletions or uniparental disomy. Conclusions: Statistically significant measures could not be reported here due to the small sample size. However, the findings show that STR instability is not a rare event in non-Hodgkin B-cell lymphomas; therefore, further detailed analysis of extended patient cohorts to determine its clinical significance is required.