Introduction: Genome instability and high mutation rate are typical features of diffuse large B-cell lymphoma (DLBCL), facilitating the rapid tumor evolution and acquisition of therapy resistance. This research aims to identify in what way the shifts in microRNA (miRNA) expression pattern can contribute to the DNA damage and genome instability. Methods: MiRNA targets within gene transcripts were predicted in sil- ico using the TargetScan software. Results: MiRNAs miR-17, miR-18, miR-19, miR-20, miR-21, miR-29, miR-92, miR-106, miR-144, miR-146, miR-155, miR-221/222, miR- 363, miR-500 and miR-574, hyperexpression of which is essential for DLBCL cells, can target transcripts of genes encoding many DNA repair enzymes as well as other DNA damage response proteins that are key elements of all DNA repair systems – base excision repair (UNG, SMUG1, MBD4, TDG, OGG1, NTHL1, NEIL1/2, APEX1, LIG3, APLF), direct reversal of damages (ALKBH3), repair of DNA- topoisomerase crosslinks (TDP1/2), mismatch excision repair (MSH2/3, MLH1/3), nucleotide excision repair (RAD23B, DDB1, RPA1/3, ERCC2, GTF2H1/2/3/5, CCNH, ERCC1/4/6/8, UVSSA), homol- ogous recombination (RAD50/51/52, RAD51B/D,XRCC2, RAD54B, MRE11A, NBS1, RBBP8, EME1, GEN1) and non-homologous end- joining (XRCC6, PRKDC, LIG4, DCLRE1C, NHEJ1). Targets of the up- regulated miRNAs are also revealed in transcripts of genes encoding ATM kinase and Fanconi anemia proteins (FANCA/C/D2/E/F/G/I/M, BRCA2, BRIP1, RAD51C, BTBD12, FAAP20). In addition, down-regulation of miRNA miR-150 can contribute to the aberrant reactivation and hyperexpression of AICDA gene, encoding cytidine deaminase AID, because its transcript carries targets of this miRNA. Also, down-regulation of anti-onco-miRNAs (e.g. miR-15/16, miR-34, miR-145 and miR-150) allows overexpression of genes encoding the factors NF-kB, SP1, HoxC4, TCF3, Stat6, Id2/3, which are AICDA transcription activators. On the contrary, tumors have indolent course if AID cannot be reactivated. For instance, MALToma cells hyperexpress miRNA miR-150, high conservative binding sites of which are revealed in transcript of AICDA gene. It can be assumed, that AID can cause even the target damage (endogenous gene knock- out) of tumor suppressor genes (incl. genes of anti-onco-miRNAs) in result of mutations in single-stranded R-loop that arises from DNA duplex during the transcription. Conclusions: MiRNAs, hyperexpression of which is essential for abnormal proliferation and surviving of DLBCL cells, silence also genes encoding DNA repair enzymes as well as other key elements of the DNA damage response network. Therefore, shifts in miRNA signature can contribute to increase of genomic instability and mutation rate, leading on the whole to oncogene abnormalities and damage of tumor suppressor genes. This process underlies the tumor evolution as well as drug resistance acquisition. Keywords: diffuse large B-cell lymphoma (DLBCL); microRNA. 297 COMPARISON OF OUTCOMES BETWEEN PATIENTS WITH MYC REARRANGED DLBCL AND DOUBLE/ TRIPLE HIT HIGH-GRADE B CELL LYMPHOMA: A PAN-LONDON RETROSPECTIVE REVIEW D. El-Sharkawi 1 | S. Sharma 1 | L. Cook 2 | B. Hanley 2 | R. Johnston 3 | A. Arasaretnam 3 | I. Lazana 4 | P. Greaves 5 | A. Parkinson 5 | Y. Peng 6 | S. Kassam 4 | V. Peacock 4 | R. Kaczmarski 7 | M. Bower 8 | B. Cheung 9 | C. De Lord 10 | M. Cross 1 | K. Vroobel 11 | A. Wotherspoon 11 | F. Aldridge 12 | J. Khwaja 13 | B. Sharma 14 | K. Cwynarski 13 | R. Pettengell 6 | I. Chau 15 | D. Cunningham 15 | K. Naresh 16 | S. Iyengar 1 1 Haematology, Royal Marsden Hospital, Sutton, United Kingdom; 2 Haematology, Hammersmith Hospital, London, United Kingdom; 3 Haematology, Royal Sussex County Hospital, Brighton, United Kingdom; 4 Haematology, King's College Hospital, London, United Kingdom; 5 Haematology, Queen's Hospital, Romford, United Kingdom; 6 Haematology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom; 7 Haematology, Hillingdon Hospital, Uxbridge, United Kingdom; 8 Haematology, Chelsea and Westminster Hospital, London, United Kingdom; 9 Haematology, Croydon University Hospital, Croydon, United Kingdom; 10 Haematology, St Helier Hospital, Carshalton, United Kingdom; 11 Histopathology, Royal Marsden Hospital, Sutton, United Kingdom; 12 Clinical Cytogenetics, Royal Marsden Hospital, Sutton, United Kingdom; 13 Haematology, University College Hospital, London, United Kingdom; 14 Radiology, Royal Marsden Hospital, Sutton, United Kingdom; 15 Department of Medicine, Royal Marsden Hospital, Sutton, United Kingdom; 16 Histopathology, Hammersmith Hospital, Hammersmith, United Kingdom Introduction: Diffuse large B cell lymphoma (DLBCL) is a clinically het- erogeneous disease. Increasing emphasis is being placed on the prog- nostic impact of tumour biology to identify groups at highest risk of treatment failure. Chromosomal rearrangements enhancing the activ- ity of the MYC proto-oncogene (MYCr) have been linked to adverse outcomes although some studies suggest that cases harbouring addi- tional translocations affecting BCL2, BCL6 or both, have the worst outcomes. There is currently no consensus on the management of MYCr, ‘double-hit’ (DH) and ‘triple-hit’ (TH) cases. Retrospective data suggests that whilst treatment intensification is associated with an improved PFS, it does not translate to an improved overall survival (OS). Moreover recent evidence suggests that the MYC translocation partner may be important in prognostication. We aimed to capture the trends in current management of patients with these high risk alterations in a pan-London retrospective study. Methods: DLBCL patients with MYCr, DH or TH were identified at 9 London centres. Demographics, cytogenetics, treatment and out- comes were obtained from patient records and anonymised data was submitted for analysis. OS was defined as survival from date of diag- nosis until death, censored at last follow-up. Median OS and follow- up time were calculated using the Kaplan Meier (KM) and reverse KM 348 ABSTRACT