ABCL-371 STR Loci Allele Imbalance at 9p24.1 in Primary Mediastinal B-Cell Lymphoma

Abstract

Molecular factors that determine the prognosis of immunotherapy response in primary mediastinal B-cell lymphoma (PMBCL) are not yet described. PD-L1/L2 expression levels in tumor samples have demonstrated clinical utility for many solid tumors. PD-L1/L2 expression levels could be affected by chromosomal lesions on 9p24.1 (losses or gains). Short tandem repeat (STR) analysis of appropriate markers is the simplest way to detect these lesions. To analyze possible associations between STR loci allele imbalance (AI) on 9p24.1 and PD-L1 expression levels in tumor cells from PMBCL patients. Two STR Loci (gt) n and (ttat)m on 9p24.1 in tumor cells were analyzed for a cohort of 36 PMBCL patients admitted to the National Medical Research Center for Hematology (Moscow, Russia) from 2013 to 2022. For six patients, STR data were compared with PD-L1 expression assessed by immunohistochemistry. 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 analysis for AI was performed by PCR with original primers. The fragment analysis was performed on an ABI3130 Genetic Analyzer. Inclusion criteria: de novo diagnosed PMBCL patients. pretreatment. The heterozygosity level for the (gt)n locus was 31 of 36 patients (86%), and AI was found in 16 of 31 (51.6%). The heterozygosity level for the (ttat)m locus was 20 of 36 patients (56%), and AI was found in 9 of 20 (45%). One patient was homozygous for both loci. No patients were found with AI at one locus and a normal heterozygous variant at the second locus. PD-L1 expression in tumor cells was evaluated for six patients. In two patients with aberrant STR loci, PD-L1 expression was found in 75%-100% of tumor cells. None of the four patients with normal 9p24.1 STR markers had PD-L1-positive cells. The high incidence of AI in the 9p24.1 locus indicates its possible involvement in the pathogenesis of PMBCL. The association between AI and PD-L1 expression in tumor cells requires confirmation in an extended cohort of patients. This study was supported by Rakfond grant 2/2020.