Contributions
Abstract: PB2335
Type: Publication Only
Background
Primary Central Nervous System Lymphoma (PCNSL) is a distinct subtype of extranodal non-Hodgkin lymphoma (NHL) confined to the brain, leptomeninges, eyes and spinal cord. It accounts for approximately 1% of all lymphomas and 3% of all brain tumours and has a dichotomous, frequently poor outcome despite recent novel treatment approaches. Specific antigen (Ag) recognition by PCNSL tumour cells through their B cell receptors (BCR) has recently been reported. Further, evidence for Ag selection and drive of the BCR of PCNSL cells is shown by marked restricted immunoglobulin heavy chain variable gene (IGHV) usage. Activation induced deaminase (AID), required for both class switching and somatic hypermutation (SHM) of the BCR, is oncogenic in NHL. Evidence for AID activity in PCNSL is demonstrated by marked and ongoing SHM of the BCR and mutations in oncogenes that show aberrant SHM mutation patterns.
Aims
Investigate the role of AID in PCNSL.
Methods
We have reviewed AID expression by immunohistochemistry (IHC) in 38 PCNSL biopsies. Additionally we successfully analysed the IGHV of some of these biopsies using the LymphoTrack® Dx IGH FR1 assay (Invivoscribe).
Results
We have demonstrated ongoing expression (positive/focal) in 24 of which 23 also express MYC protein (>30% positive cells). AID negative biopsies lack MYC positivity in 9 of 14 of cases, overall showing a strong correlation between AID and MYC (p=0.0001, Fischer’s exact test). In three PCNSL biopsies further analysed we have found that transition mutations in or near WRCY motifs, typical of an AID mutation footprint, predominate (80% mutations found, n=10).
Conclusion
This data supports a role for AID mediated antigenic drive in the pathogenesis of PCNSL with a strong correlation to MYC, a recognised tumour driver. Further work is required to explore the role of the tumour microenvironment and potential antigens.
Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research
Keyword(s): Microenvironment, Non-Hodgkin's lymphoma
Abstract: PB2335
Type: Publication Only
Background
Primary Central Nervous System Lymphoma (PCNSL) is a distinct subtype of extranodal non-Hodgkin lymphoma (NHL) confined to the brain, leptomeninges, eyes and spinal cord. It accounts for approximately 1% of all lymphomas and 3% of all brain tumours and has a dichotomous, frequently poor outcome despite recent novel treatment approaches. Specific antigen (Ag) recognition by PCNSL tumour cells through their B cell receptors (BCR) has recently been reported. Further, evidence for Ag selection and drive of the BCR of PCNSL cells is shown by marked restricted immunoglobulin heavy chain variable gene (IGHV) usage. Activation induced deaminase (AID), required for both class switching and somatic hypermutation (SHM) of the BCR, is oncogenic in NHL. Evidence for AID activity in PCNSL is demonstrated by marked and ongoing SHM of the BCR and mutations in oncogenes that show aberrant SHM mutation patterns.
Aims
Investigate the role of AID in PCNSL.
Methods
We have reviewed AID expression by immunohistochemistry (IHC) in 38 PCNSL biopsies. Additionally we successfully analysed the IGHV of some of these biopsies using the LymphoTrack® Dx IGH FR1 assay (Invivoscribe).
Results
We have demonstrated ongoing expression (positive/focal) in 24 of which 23 also express MYC protein (>30% positive cells). AID negative biopsies lack MYC positivity in 9 of 14 of cases, overall showing a strong correlation between AID and MYC (p=0.0001, Fischer’s exact test). In three PCNSL biopsies further analysed we have found that transition mutations in or near WRCY motifs, typical of an AID mutation footprint, predominate (80% mutations found, n=10).
Conclusion
This data supports a role for AID mediated antigenic drive in the pathogenesis of PCNSL with a strong correlation to MYC, a recognised tumour driver. Further work is required to explore the role of the tumour microenvironment and potential antigens.
Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research
Keyword(s): Microenvironment, Non-Hodgkin's lymphoma