Presentation on theme: "A comparison of the frequency of common lymphoma- associated gene rearrangements among B-Post transplant lymphoproliferative disorders (B-PTLD), B-cell."— Presentation transcript:
A comparison of the frequency of common lymphoma- associated gene rearrangements among B-Post transplant lymphoproliferative disorders (B-PTLD), B-cell HIV- lymphomas and diffuse large B-cell lymphoma in immune competent patients (iDLBCL). Hazem AH Ibrahim, Michael J Neat, Mufaddal Moonim, Amen Furrat, Lia Menasce, Sabine Pomplun, Margaret Burke, Donald Macdonald, Ed Kanfer, Mark Bower, Paul Fields, Nicola Foot, Alistair Reid and Kikkeri N Naresh. Department of Histopathology & Cytopathology, Hammersmith Hospital Imperial College London
20-40% of iDLBCL and HIV-related DLBCLs harbour BCL6 rearrangement that are very rarely seen in PTLDs. Post-transplant Burkitt lymphomas (PT-BL), similar to HIV-BL and iBL, display chromosomal breaks at 8q24 involving the c-MYC oncogene. Very few reports investigated chromosomal translocations among PTLDs
Do common lymphoma-associated gene rearrangements differ among B-PTLDs, B-cell HIV- lymphomas and iDLBCL?
Materials & Methods
H&E ISH Serial sections TMA FISH IHC Tissue microarray 64 B-PTLD 41 HIV-BCL 139 iDLBCL Cases collected BCL2, BCL3, BCL6, c-MYC, PAX5, MALT1 and IGH Genes investigated
Percentage involvement of rearrangements of different genes among DLBCLs in different settings HIV-DLBCL(39cases) PTLD-DLBCL(24 cases) iDLBCL (139 cases)
BCL2 and BCL6 rearrangements were predominantly restricted to GC and AGC/non-GC subtypes respectively. 8% PT-DLBCLs and 30% HIV-DLBCLs showed c- MYC rearrangement. PT-DLBCLs and HIV-DLBCLs lacked BCL2 and BCL6 rearrangements. Seven iDLBCLs (5%) and 2 HIV-DLBCLs (8%) had rearrangements of two oncogenes.
Among Burkitt lymphoma (BL), 2/2 PT-BL and 12/13 (92%) HIV-BL had c-MYC rearrangement. Among plasmablastic lymphoma (PL), 2/6 (33%) PT-PL and 1/2 HIV-PL had c-MYC rearrangement.
Rearrangements of different genes among iDLBCL subsets
EBV-association was noted in 6%, 67% and 54% of iDLBCLs, PT-DLBCLs and HIV-DLBCLs respectively. 100% PT-BL and 63% HIV-BL had EBV-association. 83% PT-PL and 100% HIV-PL had EBV-association. EBV association
None of the cases with either BCL2 or BCL6 rearrangement showed EBV-association (p=0.031 & p<0.001 respectively). No significant correlation between EBV- association and c-MYC or IGH rearrangement. Correlation of rearrangements of c-MYC, BCL2 and BCL6 genes among the EBV-positive cases
1- Gene rearrangements Gene rearrangement, apart from c-MYC-IGH (characteristically seen in BL and PL), appear to be very rare among both HIV-BCL and B- PTLD. HIV-DLBCL is more frequently associated with c-MYC rearrangement than iDLBCL. BCL6 rearrangement is frequently seen in iDLBCL of AGC and non-GC subtypes. None of the cases with either BCL2 or BCL6 rearrangement showed EBV-association.
2- Alternate pathogenetic pathways in immune deficiency LPDs Other (cyto)genetic abnormalities that are that are not conventionally associated primary abnormalities in lymphomas Aberrant somatic hypermutation of critical genes. Aberrant hypermethylation of critical genes.
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Acknowledgements Prof. Kikkeri Naresh Prof. Gordon Stamp. Dr Roberto Dina Mahrokh Nohdani. Donna Homcastle, Pritesh Trivedi, Tyler Lloyd & Kay Elderfield. William Mathieson John Brennan and David Peston. Prof. Letizia Foroni, Alistair Raid, and Jamshid Sorouri. The Egyptian Government All members of the Department of Histopathology, of Hammersmith Hospital.