ZFHX3 AND ARID1A SNPS ASSOCIATED WITH SUSCEPTIBILITY LYMPHOMA

Abstract

Non-Hodgkin lymphoma (NHL) is one the most prevalent haematological malignancies worldwide, and it is classified into more than 60 subtypes. The aetiology of NHL is still enigmatic however, some factors have been proven to be associated with NHL. Epstein-Barr virus (EBV) also called gamma herpesvirus is one of the herpes virus family. It is one of the first virus that has been directly associated with several malignancies in human including Burkitt’s lymphoma. The EBV nuclear antigen 1 (EBNA1) is one of the viral proteins and it is the only latent protein consistently expressed in viral-associated malignancies. EBNA1 plays an essential role in viral genome replication and cell division during latent infection. Additionally, it has been found that EBNA1 has an impact on cellular protein and pathways that are important to the viral survival. A previous study shows two strains transgenic mice expressing EBNA1 in B-cells develop B-cell lymphoma. These mice show the same incidence rate but has different onset depending on the genetic background of the mouse. To be specific, C57Bl/6 mice strain develop lymphoma at earlier ages compared to FVB strain mice. This indicates that the C57Bl/6 strain might carry lymphoma susceptibility alleles, or alternatively, the FVB strain, might have protective/resistance alleles. A variety of genes have been identified to be involved lymphomagenesis such as Id3, TCF3, ZFHX3 and ARID1A. In this project we will select a number of potential single nucleotide polymorphisms (SNPs) in one of the previous genes. We will design a SNP assay based on a PCR procedure to genotype tissue samples for these particular loci. Tissues source will be hybrid C59Bl/6 and FVB mice expressing EBNA1, derived from mice that developed lymphoma at different age onset.