Program: Oral and Poster Abstracts
Session: 622. Non-Hodgkin Lymphoma: Biology, excluding Therapy: Poster I
Methods: Genomic DNA was extracted from FFPE/FF splenic tumor or bone marrow samples. When available, DNA from oral mucosa was obtained as the corresponding non-tumor control. Whole exome sequencing was performed at CNAG (Barcelona, Spain) following standard protocols for high-throughput paired-end sequencing on the Illumina HiSeq2000 instruments (Illumina Inc., San Diego, CA). Validation of variants was performed by PCR based targeted resequencing using a MiSeq instrument (Illumina Inc., San Diego, CA).
We performed paired-end-76pb whole exome sequencing on DNA from 15 SDRPL patients. The corresponding normal counterpart from 3 of the patients was sequenced. From one patient FFPE and bone marrow DNA was available for comparison. In total 9 FFPE tissue samples, 3 FF tissue samples, and 4 bone marrow samples were sequenced. Almost 95% of the selected variants were validated by PCR based resequencing in 9 of the patients, while from 6 of the patients no tissue was available for validation
Results: 290 substitutions and 26 indels were obtained after filtering. Whole exome sequencing permitted us to identify variations in several genes of relevant pathways in lymphomas, such as NFkB pathway (IkBKB, TRAF, TANK, SYK), Apoptosis (BAD, DCPS, BCLAF1), MAPK (CXCR4, TCF3, NF1, MAP3K5), Cell cycle (CCND3, POLD3, BUB1), Chromatin (CREBBP, ARID1A, ARID1B, ARID3A, MLL3), MYC regulators (AKAP10, CTCF, EP400) or WNT signaling (SALL1, WNT5B, GPC6). Moreover, CCND3 and MLL3 were recurrently mutated in 2 different patients. Genes specifically found mutated in other splenic malignancies, such as NOTCH2, BRAF, MAP2K1, and KLF2 were not found mutated in this series of SDRPL patients.
Conclusions: SDRPL samples contain somatic mutations involving genes regulating relevant pathways for cell survival, such as NFkB, apoptosis, cell cycle, chromatin, or WNT. The mutational signature of the series studied here may indicate that SDRPL is a distinct entity with specific molecular features different to other lymphoid splenic malignancies.
Disclosures: No relevant conflicts of interest to declare.
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