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Correction: Shyamsunder et al. THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors. <i>Int. J. Mol. Sci.</i> 2022, <i>23</i>, 1207.

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Related Experiment Video

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Analyzing Tumor Gene Expression Factors with the CorExplorer Web Portal

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Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma.

Michal Marek Hoppe¹, Patrick Jaynes¹, Fan Shuangyi²

¹Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Cancer Discovery

|April 18, 2023

Summary

Specific oncogene combinations in cancer cells, like MYC+BCL2+BCL6-, predict patient survival. This finding from diffuse large B-cell lymphoma (DLBCL) research may improve cancer prognostication and treatment strategies.

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Area of Science:

Oncology
Molecular Biology
Genetics

Background:

Cancers frequently overexpress multiple oncogenes.
The impact of oncogene combinations within cancer cell subpopulations on clinical outcomes remains unclear.
Diffuse large B-cell lymphoma (DLBCL) serves as a model for investigating oncogene coexpression.

Purpose of the Study:

To investigate if specific combinations of oncogenes in cellular subpopulations within DLBCL influence patient survival.
To develop a method for estimating cellular oncogenic coexpression from standard clinical data.
To identify molecular regulators associated with unfavorable oncogenic coexpression patterns.

Main Methods:

Quantitative multispectral imaging of MYC, BCL2, and BCL6 oncogenes in DLBCL tissues.
Analysis of four independent patient cohorts (n=449) and validation in immunohistochemistry (n=316) and gene expression (n=2,521) datasets.
Comparative bulk and single-cell transcriptomic analyses of DLBCL samples and engineered B cells.

Main Results:

A unique combination, MYC+BCL2+BCL6- (M+2+6-), consistently predicted survival across cohorts.
The percentage of M+2+6- cells could be mathematically derived and correlated with survival.
Cyclin D2 and PI3K/AKT pathways were identified as potential regulators of the M+2+6- phenotype.

Conclusions:

Specific oncogene combinations in subpopulations, particularly M+2+6-, are significant prognostic markers in DLBCL.
A probabilistic metric for oncogenic coexpression estimation has implications for prognostication and therapeutic target discovery.
Further research into oncogenic combinations at single-cell resolution may enhance understanding of cancer evolution and resistance.