ABCL-261: STR Profiling Reveals Tumor Genome Instability in Primary Mediastinal B-Cell Lymphoma

Abstract

<h3>Context</h3> Molecular factors to determine the prognosis for primary mediastinal B-cell lymphoma (PMBCL) are not described yet. In this regard, the loss of heterozygosity (LOH) in STR loci and elevated microsatellite alteration at selected tetranucleotides (EMAST) in the tumor genome are of interest. <h3>Objective</h3> To analyze the frequency of LOH and EMAST in tumor cells of PMBCL patients at diagnosis and to check possible association with disease features. <h3>Design</h3> STR profiles of the DNA of tumor cells were analyzed in a cohort of 72 PMBCL patients undergoing EPOCH regimen treatment at the National Research Center for Hematology (Moscow, Russia). <h3>Setting</h3> DNA was isolated from tumor biopsy samples taken at diagnosis. Control DNA samples were taken from the blood of patients in complete remission or from the buccal epithelium. STR profiles for LOH and EMAST analysis were assessed by PCR with the COrDIS Plus multiplex kit for amplification of 19 STR markers and amelogenin loci (Gordiz Ltd, Russia). The fragment analysis was performed on an ABI3130 Genetic Analyzer. <h3>Patients</h3> Inclusion criterion: <i>de novo</i>-diagnosed PMBCL patients. Exclusion criterion: pre-treatment. <h3>Main Outcomes Measures</h3> Progression-free survival (PFS) and overall survival (OS) at 24 months from diagnosis were used to assess the independent impact of genetic instability as a risk factor. <h3>Results</h3> LOH was detected in 37 of 72 patients (51.4%). EMAST was found in 40 patients (55.5%); 24 had a combination of EMAST with LOH. For all EMAST-positive patients, the number of involved loci was no more than 4 out of 19 (EMAST-low, less than one-third of the panel of microsatellite markers). It was shown that OS and PFS were the highest in patients with a stable STR tumor profile. <h3>Conclusions</h3> STR profiling of PMBCL tumor genome revealed LOHs associated with deletions or uniparental disomy and detected EMAST attributed to failure of DNA mismatch repair. The high incidence of LOH and EMAST in PMBCL can be associated with standard therapy failure in a significant number of patients. <h3>Funding</h3> This study was supported by Rakfond grant 2/2020.