| Autor: |
Rashid, Mamoon, Ali, Rizwan, Almuzzaini, Bader, Song, Hao, AlHallaj, Alshaimaa, Abdulkarim, Al Abdulrahman, Mohamed Baz, Omar, Al Zahrani, Hajar, Mustafa Sabeena, Muhammed, Alharbi, Wardah, Hussein, Mohamed, Boudjelal, Mohamed |
| Předmět: |
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| Zdroj: |
Cancer Medicine; Nov2021, Vol. 10 Issue 22, p8138-8150, 13p |
| Abstrakt: |
The colony stimulating factor 2 receptor subunit beta (CSF2RB) is the common signaling subunit of the cytokine receptors for IL‐3, IL‐5, and GM‐CSF. Several studies have shown that spontaneous and random mutants of CSF2RB can lead to ligand independence in vitro. To date, no report(s) have been shown for the presence of potentially transforming and oncogenic CSF2RB mutation(s) clinically in cancer patients until the first reported case of a leukemia patient in 2016 harboring a germline‐activating mutation (R461C). We combined exome sequencing, pathway analyses, and functional assays to identify novel somatic mutations in KAIMRC1 cells and breast tumor specimen. The patient's peripheral blood mononuclear cell (PBMC) exome served as a germline control in the identification of somatic mutations. Here, we report the discovery of a novel potentially transforming and oncogenic somatic mutation (S230I) in the CSF2RB gene of a breast cancer patient and the cell line, KAIMRC1 established from her breast tumor tissue. KAIMRC1 cells are immortalized and shown to survive and proliferate in ligand starvation condition. Immunoblot analysis showed that mutant CSF2RB signals through JAK2/STAT and PI3K/mTOR pathways in ligand starvation conditions. Screening a small molecule kinase inhibitor library revealed potent JAK2 inhibitors against KAIMRC1 cells. We, for the first time, identified a somatic, potentially transforming, and oncogenic CSF2RB mutation (S230I) in breast cancer patients that seem to be an actionable mutation leading to the development of new therapeutics for breast cancer. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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