Analysis of Genetic Alterations in Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma With Whole-Exome Sequencing

Abstract

Next-generation sequencing studies on ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML) have to date revealed several targets of genetic aberrations. However, most of our current understanding of the pathogenesis and prognosis of OAML is primarily based on studies conducted in populations from Europe and the US. Furthermore, the majority were based on formalin-fixed paraffin-embedded (FFPE) tissue, which generally has poor integrity and creates many sequencing artifacts. To better investigate the coding genome landscapes of OAML, especially in the Chinese population, we performed whole-exome sequencing of 21 OAML cases with fresh frozen tumor tissue and matched peripheral blood samples. IGLL5, as a novel recurrently mutated gene, was found in 24% (5/21) of patients, with a higher relapse rate (P=0.032). In addition, mutations of MSH6, DIS3, FAT1, and TMEM127 were found in 10% of cases. These novel somatic mutations indicate the existence of additional/alternative lymphomagenesis pathways in OAML. Moreover, the difference between our and previous studies suggests genetic heterogeneity of OAML between Asian and Western individuals.

Transcriptomic analysis of mRNAs in human whole blood identified age-specific changes in healthy individuals

“…IGLL5, encoding one of the immunoglobulin lambda-like polypeptides, frequently occurs in the mutation in cancer, including lymphoma, multiple myeloma, and chronic lymphoblastic leukemia. [20][21][22] Although the mutation rate of IGLL5 did not change with age, [23] Yao et al have shown that the low expression level of IGLL5 is a good diagnostic in elderly patients with late-onset major depressive disorder which increases the risk of suicide and disability in olds. [24] Therefore, we speculated that IGLL5 has a vital role in staying healthy for elders.…”

Novel Insights into Pathophysiology of Orbital Inflammatory Diseases and Progression to Orbital Lymphoma by Pathway Enrichment Analysis

“…This pathway being one of the prominent activated pathways in the IgG4-ROD group supports the hypothesis of microorganisms being a conductor in the activation of inflammation leading to a chronic disease that exacerbates in IgG4-immunopositive plasma cell infiltration [ 50 ]. Furthermore, a recent next-generation sequencing study of orbital MALT lymphoma in an Asian population revealed a higher occurrence of somatic mutations in the NOD-like receptor signaling pathway, suggesting its importance in the oncogenesis [ 51 ].…”