Intragenic β-synuclein rearrangements in malignancy

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Synucleins (alpha, beta, gamma) are neuronal proteins.
• Mutations in alpha- and beta-synuclein are linked to neurodegenerative diseases.
• Synuclein upregulation correlates with poor prognosis and drug resistance in various cancers.

Purpose of the Study:

• To report novel rearrangements of beta-synuclein.
• To investigate the potential role of rearranged beta-synuclein in tumorigenesis.

Main Methods:

• Case study of pediatric T-cell acute lymphoblastic leukemia (T-ALL) with beta-synuclein rearrangement.
• Analysis of The Cancer Genome Atlas (TCGA) database for lung cancer cases.
• In-frame fusion of beta-synuclein (SNCB) with ETV6 identified in T-ALL.

Main Results:

• A novel in-frame rearrangement of beta-synuclein (SNCB) with ETV6 was found in a pediatric T-ALL case.
• Another beta-synuclein rearrangement was identified in lung squamous cell carcinoma via TCGA data.
• Both rearrangements involved the C-terminal region of beta-synuclein.

Conclusions:

• Rearranged beta-synuclein may contribute to cancer development by deregulating apoptosis, similar to alpha-synuclein.
• Overexpression of synucleins suggests a role in cell proliferation, implying rearranged beta-synuclein could affect the cell cycle.