814MO - Molecular biology study of primary immuno-privileged lymphomas

Background

Primary immune-privileged lymphoma, a rare subtype newly classified in the 5th WHO edition, primarily arises in immune-privileged locales like the central nervous system (CNS), testes, and vitreoretinal regions. Limited research exists on whether organ-specific extranodal lymphomas share molecular biological characteristics or immune environments. The main aim of our study is to seek to identify genetic alterations and oncogenic pathways specific to these lymphomas and explore their similarities and differences.

Methods

First, we will perform target-exome sequencing (TES) (from available data in Phoenix trial) or whole-exome sequencing (WES) (from multicenter retrospective specimen in China), whole genome sequencing (WGS), and RNA sequencing to identify genetic alterations and expression profiles specific and genetic subtype to CNS, testes, breast, and lymph nodes. Second, we will use bioinformatics tools to analyze the data.

Results

In this study, a total of 286 cases of DLBCL from four centers were included, including 192 cases of IP-LBCL (comprising 125 cases of primary testicular and 67 cases of primary central nervous system, and 94 cases of primary breast DLBCL. In terms of molecular biology, this study conducted whole exome sequencing (WES) on 139 cases of DLBCL and whole genome sequencing (WGS) on 127 cases, including 62 cases of IP-LBCL and 64 DLBCL controls. The gene mutation spectrum of IP-LBCL was similar to that of breast DLBCL. Compared with systemic DLBCL, MYD88, CD79B, PIM1, IGLL5, and OSBPL10 were common high-frequency recurring genes in all three subtypes. According to molecular subtyping based on self-developed optimized algorithms, IP-LBCL and breast DLBCL were mainly classified into MCD and BN2 subtypes. The prognosis of the BN2 subtype was relatively better, with 5-year PFS and OS rates of 61.00% and 81.45%, respectively. The combined 5-year PFS and OS rates for other subtypes were 54.81% and 73.94%, respectively.

Conclusions

IP-LBCL and breast DLBCL exhibit unique clinical and pathological features, with generally poor prognoses, especially for those originating CNS. The molecular and biological features identified offer potential therapeutic targets for IP-LBCL and breast DLBCL.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.