GENETICALLY DISTINCT PATHOGENESIS OF EPSTEIN‐BARR VIRUS (EBV)‐POSITIVE VERSUS EBV‐NEGATIVE CLASSICAL HODGKIN (CHL) LYMPHOMA.

In particular (Figure A): (i) JAK-STAT signaling genes STAT6, SOCS1, CSF2RB and JAK2 were mutated in 85% EBV- versus 47% EBV+ cases ( I p i = 0.0057); (ii) PI3K-AKT signaling genes GNA13 and ITPKB were mutated in 34% EBV- versus 7% EBV+ cases ( I p i = 0.047); and (iii) NF- B signaling genes TNFAIP3, NFKBIE and REL were mutated in 85% EBV- versus 47% EBV+ cases ( I p i = 0.0057). Tumor and normal cells were purified from frozen samples by microdissection ( I n i = 39; 9 EBV+, 30 EBV-) or flow cytometry ( I n i = 18; 7 EBV+, 11 EBV-). EBV- cHL had also more frequent mutations of the MHC-I genes B2M and HLA-A/B/C (56% vs. 20% in EBV+ cHL, I p i = 0.0032; Figure A), possibly to prevent presentation of tumor neo-antigens generated by the much higher mutation burden. [Extracted from the article]