RASSF4 Silencing Promotes RAS-Driven Progression in Multiple Myeloma

Scientific Contributions by Alboukadel Kassambara

This study demonstrates that loss of RASSF4 expression, driven by promoter methylation, promotes multiple myeloma progression and resistance. RASSF4 reactivation re-sensitizes cells to MAPK and proteasome-targeted therapy.

Scientific Abstracts
Author
Affiliation
Published

March 1, 2018

Modified

May 21, 2025

Keywords

Alboukadel Kassambara, RASSF4, multiple myeloma, methylation, GenomicScape, gene expression, bortezomib, trametinib, Cancer Research

De Smedt E, Maes K, Verhulst S, Lui H, Kassambara A, Maes A, Robert N, Heirman C, Cakana A, Hose D, Breckpot K, van Grunsven LA, De Veirman K, Menu E, Vanderkerken K, Moreaux J, De Bruyne E. Loss of RASSF4 Expression in Multiple Myeloma Promotes RAS-Driven Malignant Progression. Cancer Research. 2018. Download the PDF

Summary of the Study

RASSF4, a pro-apoptotic RAS effector, is frequently silenced in cancers but its role in multiple myeloma (MM) was previously unknown. This study demonstrates that RASSF4 loss contributes to RAS-driven MM progression and drug resistance.

Key findings

  • RASSF4 downregulation correlates with disease progression and worse prognosis

  • Promoter methylation of RASSF4 is associated with transcriptional silencing and can be reversed by epigenetic drugs

  • RASSF4 overexpression:

    • Induces G2 arrest and apoptosis
    • Enhances sensitivity to bortezomib
    • Potentiates the effect of trametinib (MEK1/2 inhibitor)
  • Combined kinase and epigenetic targeting showed synergistic anti-MM activity

Important

In this study, Alboukadel Kassambara contributed to the bioinformatic analysis of promoter methylation and provided GenomicScape access for gene expression profiling and survival association analysis of RASSF4 in multiple myeloma.

Citation

Publication: In Cancer Research
Date: March 1, 2018
Type: Journal Article
PDF: Download the PDF

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Scientific Contributions

Note

Here are more scientific abstracts authored or co-authored by Alboukadel Kassambara. These contributions span computational biology, bioinformatics, biostatistics, machine learning, and multi-omics, with a focus on immuno-oncology and translational research.

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