# The role of  a novel fusion oncogene FYN-TRAF3IP2 in peripheral T-cell lymphoma

> **NIH NIH F30** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $50,520

## Abstract

Project Summary
Peripheral T-cell lymphomas (PTCL) are highly aggressive lymphoid tumors derived from post-thymic mature
T-cells. Accounting for 10-15% of non-Hodgkin lymphomas of North America with increasingly more people
being diagnosed with the disease, PTCL is associated with dismal prognosis of 5 year survival rate at about
30%. The scarcity of information on driver oncogenes and their contribution to the lymphomagenesis has
further hindered the identification of therapeutic targets, underscoring the need to identify the elusive
mechanisms of PTCL tumorigenesis. This project aims to analyze oncogenic role and mechanisms of FYN-
TRAF3IP2, a novel recurrent PTCL fusion oncogene identified via RNA sequencing analyses. Fyn is a SRC
family tyrosine kinase with a crucial role in T-cell receptor (TCR) signaling, while TRAF3IP2 is a signaling
adaptor protein implicated in canonical NF-κB activation. FYN-TRAF3IP2 fusions are composed of the N-
terminal regulatory regions of Fyn kinase and the signaling and protein-protein interaction domains of the
TRAF-interacting protein 2 (TRAF3IP2) adaptor protein. Of note, TCR signaling and NF-κB activation are both
important regulators of cell proliferation and survival in PTCL lymphoma. I have demonstrated that FYN-
TRAF3IP2 fusions induce increase in NF-κB signaling in response to protein kinase C (PKC) activation, which
endogenously follows TCR activation in T-cells. My central hypothesis is that FYN-TRAF3IP2 deregulates NF-
κB signaling in T-cell progenitors promoting activation of downstream effector pathways implicated in
lymphoma transformation. Here I will formally explore the mechanisms of T-cell transformation by FYN-
TRAF3IP2 in PTCLs. Specifically: (i) investigate the functional consequences of FYN-TRAF3IP2 expression in
TCR signaling, cell growth, proliferation and survival in primary T-cells; (ii) identify the biochemical
mechanisms mediating NF-κB activation by FYN-TRAF3IP2; and (iii) analyze the oncogenic role of FYN-
TRAF3IP2 in T-cell transformation in vivo.

## Key facts

- **NIH application ID:** 9850554
- **Project number:** 5F30CA225052-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Christine Sheila Moon
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850554

## Citation

> US National Institutes of Health, RePORTER application 9850554, The role of  a novel fusion oncogene FYN-TRAF3IP2 in peripheral T-cell lymphoma (5F30CA225052-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850554. Licensed CC0.

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