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Published on: December 28, 2015
STR Profiling Reveals Tumor Genome Instability in Primary Mediastinal B-Cell Lymphoma
Natalya Risinskaya1, Yana Mangasarova1, Elena Nikulina1
1National Medical Research Center for Hematology, Ministry of Health of Russian Federation, 125167 Moscow, Russia.
Abstract:
Primary mediastinal B-cell lymphoma (PMBCL) is the only non-Hodgkin's lymphoma variant responding to immune checkpoint inhibitor (ICI) therapy, approximately in half of the cases; however, no molecular markers predicting a response to ICI therapy in PMBCL have been described so far. In this study, we assessed the incidence of the loss of heterozygosity (LOH), elevated microsatellite alteration at selected tetranucleotides (EMAST), and microsatellite instability (MSI) in the tumor genomes of 72 patients with PMBCL undergoing high-dose chemotherapy treatment at the National Research Center for Hematology (Moscow, Russia). Tumor DNA was isolated from biopsy samples taken at diagnosis. Control DNA was isolated from the blood of patients in complete remission or from buccal epithelium. STR-profiles for LOH and EMAST were assessed by PCR with COrDIS Plus multiplex kit (Gordiz Ltd., Moscow, Russia). 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. MSI-high was not found, while MSI-low was detected only in one patient. The association of certain genetic lesions with the clinical outcome in patients receiving treatment according to the standard clinical protocol R-Da-EPOCH-21 has been estimated (58 patients out of 72) and no associations with the worst overall or event-free survival were found.
Insights
This study investigated genetic markers in primary mediastinal B-cell lymphoma (PMBCL) and found no association between loss of heterozygosity (LOH) or elevated microsatellite alteration at selected tetranucleotides (EMAST) and patient survival outcomes. Microsatellite instability was not a significant factor in this cohort.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Primary mediastinal B-cell lymphoma (PMBCL) is a distinct non-Hodgkin's lymphoma subtype.
- Approximately 50% of PMBCL patients respond to immune checkpoint inhibitor (ICI) therapy.
- No predictive molecular markers for ICI response in PMBCL have been identified.
Purpose of the Study:
- To assess the incidence of loss of heterozygosity (LOH), elevated microsatellite alteration at selected tetranucleotides (EMAST), and microsatellite instability (MSI) in PMBCL.
- To investigate potential associations between these genetic alterations and clinical outcomes in PMBCL patients treated with chemotherapy.
Main Methods:
- Tumor DNA from 72 PMBCL patients was analyzed for LOH, EMAST, and MSI.
- DNA was isolated from diagnostic biopsy samples.
- Short tandem repeat (STR) profiling was performed using PCR and the COrDIS Plus multiplex kit.
Main Results:
- LOH was detected in 51.4% of patients, and EMAST in 55.5%.
- A combination of EMAST and LOH was observed in 24 patients.
- No significant association was found between LOH, EMAST, or MSI and overall or event-free survival in patients treated with R-Da-EPOCH-21 chemotherapy.
Conclusions:
- LOH and EMAST are common genetic alterations in PMBCL.
- These specific genetic markers do not appear to predict clinical outcomes in PMBCL patients receiving standard chemotherapy.
- Further research is needed to identify predictive biomarkers for ICI therapy in PMBCL.
