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Published on: June 27, 2020
Analysis of CD74 Occurrence in Oncogenic Fusion Proteins
Jasmine Vargas1, Georgios Pantouris1
1Department of Chemistry, University of the Pacific, Stockton, CA 95211, USA.
Abstract:
CD74 is a type II cell surface receptor found to be highly expressed in several hematological and solid cancers, due to its ability to activate pathways associated with tumor cell survival and proliferation. Over the past 16 years, CD74 has emerged as a commonly detected fusion partner in multiple oncogenic fusion proteins. Studies have found CD74 fusion proteins in a range of cancers, including lung adenocarcinoma, inflammatory breast cancer, and pediatric acute lymphoblastic leukemia. To date, there are five known CD74 fusion proteins, CD74-ROS1, CD74-NTRK1, CD74-NRG1, CD74-NRG2α, and CD74-PDGFRB, with a total of 16 different variants, each with unique genetic signatures. Importantly, the occurrence of CD74 in the formation of fusion proteins has not been well explored despite the fact that ROS1 and NRG1 families utilize CD74 as the primary partner for the formation of oncogenic fusions. Fusion proteins known to be oncogenic drivers, including those of CD74, are typically detected and targeted after standard chemotherapeutic plans fail and the disease relapses. The analysis reported herein provides insights into the early intervention of CD74 fusions and highlights the need for improved routine assessment methods so that targeted therapies can be applied while they are most effective.
Insights
The CD74 protein is frequently found in cancers and forms oncogenic fusion proteins. Early detection of these CD74 fusions is crucial for effective targeted therapy before disease relapse.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- CD74 is a type II cell surface receptor highly expressed in various cancers, promoting tumor cell survival and proliferation.
- CD74 has become a significant fusion partner in oncogenic fusion proteins over the last 16 years.
- CD74 fusions are implicated in lung adenocarcinoma, inflammatory breast cancer, and pediatric acute lymphoblastic leukemia.
Purpose of the Study:
- To investigate the role of CD74 in oncogenic fusion protein formation.
- To explore the potential for early intervention strategies targeting CD74 fusions.
- To emphasize the need for improved routine diagnostic methods for CD74 fusions.
Main Methods:
- Review of existing literature on CD74 fusion proteins.
- Analysis of genetic signatures of known CD74 variants.
- Discussion of therapeutic implications based on current research.
Main Results:
- Five known CD74 fusion proteins (CD74-ROS1, CD74-NTRK1, CD74-NRG1, CD74-NRG2α, CD74-PDGFRB) with 16 variants have been identified.
- CD74 is a primary fusion partner for ROS1 and NRG1 oncogenic fusions.
- Current detection and targeting of CD74 fusions often occur after treatment failure.
Conclusions:
- The formation and role of CD74 in fusion proteins require further exploration.
- Early detection and assessment of CD74 fusions are necessary for timely and effective targeted therapy.
- Improved routine assessment methods are needed to optimize the application of targeted therapies for CD74-driven cancers.
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