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    GENE:

    PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)

    i
    Other names: PREX2, Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2, Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Rac Exchanger 2 Protein, Protein Phosphatase 1, Regulatory Subunit 129, PtdIns(3,4,5)-Dependent Rac Exchanger 2, DEP Domain-Containing Protein 2, PPP1R129, DEPDC2, P-REX2, DEP.2, Phosphatidylinositol-3,4,5-Trisphosphate-Dependent Rac Exchange Factor 2, DEP Domain Containing 2, FLJ12987, P-Rex2
    24d
    Tissue-Free Circulating Tumor DNA Assay and Patient Outcome in a Phase III Trial of FOLFOX-Based Adjuvant Chemotherapy (Alliance N0147). (PubMed, J Clin Oncol)
    Evaluation of ctDNA in resected stage III CC using a tissue-free assay provided robust and independent prognostic value. Higher ctDNA burden, dMMR, and specific mutations defined poor prognostic groups among ctDNA-positive patients.
    P3 data • Journal • Circulating tumor DNA
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    FLT1 (Fms-related tyrosine kinase 1) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)
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    BRAF V600E • MSI-H/dMMR • BRAF V600
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    Erbitux (cetuximab) • 5-fluorouracil • oxaliplatin • leucovorin calcium
    4ms
    Secretory breast carcinoma: morphologic and molecular heterogeneity with indicators of aggressive potential in a cohort of 29 cases. (PubMed, J Pathol Clin Res)
    A solid-predominant pattern with increased cytological atypia, mitotic activity, and necrosis may indicate aggressive potential. Routine NTRK testing supports diagnosis and may help identify patients who could benefit from TRK-inhibitor therapy in advanced disease.
    Retrospective data • Journal
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    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • RANBP2 (RAN Binding Protein 2) • NCOR1 (Nuclear Receptor Corepressor 1) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • NTRK (Neurotrophic receptor tyrosine kinase) • NUP107 (Nucleoporin 107)
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    HER-2 negative
    4ms
    Integration of scRNA-Seq and scATAC-Seq Reveals Malignant Characteristics of Sarcomatoid Clear Cell Renal Cell Carcinoma. (PubMed, Cancer Sci)
    Moreover, we determined that PREX2 played a malignant role in ccRCC with sarcomatoid differentiation in vitro and in vivo, facilitating tumor progression by inhibiting PTEN and activating the PI3K/AKT pathway. This study demonstrated the comprehensive gene expression and DNA regulation information of ccRCC with sarcomatoid differentiation, highlighting its malignant characteristics, thereby offering novel insights for the diagnosis and treatment of sarcomatoid ccRCC.
    Journal
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    PTEN (Phosphatase and tensin homolog) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • FOSL1 (FOS Like 1) • FOSL2 (FOS Like 2)
    5ms
    Comprehensive Genomic Profiles of Melanoma in Veterans Compared to Reference Databases. (PubMed, Fed Pract)
    The melanomas found in these veterans showed a significantly higher frequency of variants in CDKN2A/B; a significantly lower frequency of variants in ROS1, GRIN2A, KDR, KMT2C (MLL3), KMT2D (MLL2), LRP1B, PTPRT, PTCH1, FAT4, and PREX2; and a significantly higher frequency of tumor mutational burdens exceeding 10 mutations/megabase. The presence of statistically significant differences between the genomic findings from the veterans' melanomas and those of general population melanomas from reference databases suggests that additional research is warranted to corroborate these differences and clarify their etiologic, prognostic, and therapeutic relevance.
    Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KDR (Kinase insert domain receptor) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • PTCH1 (Patched 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KMT2C (Lysine Methyltransferase 2C) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • PTPRT (Protein tyrosine phosphatase receptor type T) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • FAT4 (FAT Atypical Cadherin 4) • GRIN2A (Glutamate Ionotropic Receptor NMDA Type Subunit 2A)
    5ms
    Pathogenic variants reveal candidate genes for prostate cancer germline testing for men of African ancestry. (PubMed, Nat Commun)
    Besides notable impact of DNA polymerases, including POLG, Fanconi anaemia genes include FANCD2, FANCA, FANCG, ERCC4, FANCE and FANCI, while DNA mismatch repair genes MSH3 and PMS1 outranked known namesakes MSH6 and PMS2. This study provides insights into the spectrum of African-relevant potentially pathogenic PCa variants, highlighting much-needed gene candidates for ancestry-inclusive germline testing.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • LRP1B (LDL Receptor Related Protein 1B) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS2 (PMS1 protein homolog 2) • FAT1 (FAT atypical cadherin 1) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MSH3 (MutS Homolog 3) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • PMS1 (PMS1 protein homolog 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • HOXB13 (Homeobox B13)
    5ms
    Unraveling the role of PREX2 mutations as a biomarker for immunotherapy response in colorectal cancer. (PubMed, Cancer Biomark)
    Cetuximab and Bortezomib sensitivity was higher in PREX2 - mutated colorectal cancer. In gastric cancer, there are no established immune associations with PREX2 mutations.ConclusionPREX2 mutations may serve as a novel predictive biomarker for immunotherapy in CRC, potentially enhancing antitumor immunity via microenvironment modulation, but lack predictive value in GC. These findings highlight PREX2's role in refining patient stratification for immune checkpoint inhibitors.
    Retrospective data • Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)
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    TMB-H • MSI-H/dMMR
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    Erbitux (cetuximab) • bortezomib
    10ms
    AHCYL1 mediates the tumor-promoting effect of PREX2 in non-small cell lung carcinoma. (PubMed, Theranostics)
    Consequently, AHCYL1 intensifies the tumor-promoting effects of PREX2 in NSCLC. Overall, our results indicate that PREX2 and AHCYL1 promote lung cancer development and reveal a novel regulatory mechanism of PREX2 GEF activity by AHCYL1, which will contribute to the understanding of NSCLC pathogenesis and offer new targets and strategies for the diagnosis and treatment of NSCLC.
    Journal
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    PTEN (Phosphatase and tensin homolog) • RAC1 (Rac Family Small GTPase 1) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)
    1year
    Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma. (PubMed, Cancer Res)
    Importantly, genetic and pharmacological targeting of PI3Kβ phenocopied PREX2 deficiency, sensitizing model systems to therapy. These data reveal a druggable PREX2/RAC1/PI3Kβ signaling axis in BRAF-mutant melanoma that could be exploited clinically.
    Journal
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    BRAF (B-raf proto-oncogene) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)
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    BRAF V600E • BRAF V600
    over1year
    Melanoma genomics - will we go beyond BRAF in clinics? (PubMed, J Cancer Res Clin Oncol)
    We also present a comparison of genomic profiles obtained in recent years with a focus on the most common melanoma genes. Finally, we propose our melanoma gene panel consisting of 22 genes that, in our opinion, are "must-have" genes in both melanoma-specific genomic tests and pan-cancer tests established to improve the treatment of melanoma further.
    Review • Journal
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    BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NF1 (Neurofibromin 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)
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    BRAF mutation • BRAF V600
    over1year
    Unraveling druggable cancer-driving proteins and targeted drugs using artificial intelligence and multi-omics analyses. (PubMed, Sci Rep)
    This strategy effectively predicts and prioritizes biomarkers, therapeutic targets, and drugs for in-depth studies in clinical trials. Scripts are available at https://github.com/muntisa/machine-learning-for-druggable-proteins .
    Journal
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    HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • CCNE1 (Cyclin E1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2) • ACVR1 (Activin A Receptor Type 1) • CASP8 (Caspase 8) • MUTYH (MutY homolog) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C) • JAG1 (Jagged Canonical Notch Ligand 1) • VAV1 (Vav Guanine Nucleotide Exchange Factor 1) • ATG7 (Autophagy Related 7) • BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
    over1year
    Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma. (PubMed, Natl Sci Rev)
    Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted therapy. Collectively, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.
    Journal • BRCA Biomarker
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    CD8 (cluster of differentiation 8) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)
    almost2years
    PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer. (PubMed, BMC Med)
    PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.
    Journal
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    CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1) • PREX2 (Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2)