^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    BIOMARKER:

    WRN mutation

    i
    Other names: WRN, WRN RecQ Like Helicase, Werner Syndrome ATP-Dependent Helicase, Werner Syndrome RecQ Like Helicase, DNA Helicase RecQ-Like Type 3, RecQ Protein-Like 2, Exonuclease WRN, RECQL2, RECQ3, Werner Syndrome RecQ Helicase-Like, Werner Syndrome, RECQL3, RecQ3
    Entrez ID:
    7486
    Related biomarkers:
    Expression
    1m
    Dietary Restriction Fails to Extend Lifespan of Drosophila Model of Werner Syndrome. (PubMed, G3 (Bethesda))
    Compared to wild type control flies, the mutant flies also exhibited altered responses to DR in their resistance to starvation and oxidative stress, as well as changes in sleep/wake patterns. These findings show that the WRN protein is necessary for mediating the effects of DR and suggest that the exonuclease domain of WRN plays an important role in metabolism in addition to its primary role in DNA repair and genome stability.
    Journal
    |
    WRN (WRN RecQ Like Helicase)
    |
    WRN mutation
    2ms
    Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=23, Terminated, Georgetown University | Trial completion date: Jul 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Oct 2023; Lack of accrual
    Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    BARD1 mutation • WRN mutation
    |
    carboplatin • Zejula (niraparib)
    4ms
    Sclerosing epithelioid fibrosarcoma associated with WRN gene variant presenting as chronic dyspnea and pathologic cervical fracture: a case report and review of the literature. (PubMed, J Med Case Rep)
    Sclerosing epithelioid fibrosarcoma is a very rare entity, only cited approximately 100 times in literature to date. Physicians should be aware of this disease entity and consider it in their differential diagnosis. Though pulmonary involvement has been described in the context of sclerosing epithelioid fibrosarcoma, this malignancy may affect many organ systems, warranting extensive investigation. Through our diagnostic workup, we suggest a possible link between sclerosing epithelioid fibrosarcoma and the WRN gene. Further study is needed to advance our understanding of sclerosing epithelioid fibrosarcoma and its clinical associations as it is an exceedingly rare diagnosis.
    Review • Journal
    |
    MUC4 (Mucin 4, Cell Surface Associated) • WRN (WRN RecQ Like Helicase)
    |
    WRN mutation
    |
    doxorubicin hydrochloride
    5ms
    Genomic analysis of a Palestinian family with inherited cancer syndrome: a next-generation sequencing study. (PubMed, Front Genet)
    Our findings confirm that the homozygous ERCC2 (p.R683Q) mutation was responsible for causing melanoma and other cancer types in the family. Our work highlights the value to decipher the mutational background of familial cancers, especially CM, in the Palestinian population to guide diagnosis, prevention, and treatment of affected patients and their families.
    Journal • Next-generation sequencing
    |
    ERCC2 (Excision repair cross-complementation group 2) • WRN (WRN RecQ Like Helicase) • TYRP1 (Tyrosinase Related Protein 1)
    |
    WRN mutation • ERCC2 mutation
    6ms
    Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=23, Active, not recruiting, Georgetown University | Recruiting --> Active, not recruiting | N=146 --> 23
    Enrollment closed • Enrollment change • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    BARD1 mutation • WRN mutation
    |
    carboplatin • Zejula (niraparib)
    6ms
    The identification of a novel mutation (p.I223fs) in WRN associated with Werner syndrome. (PubMed, Endocrine)
    We identified a novel homozygous frameshift mutation, p.I223fs, in WRN in a Chinese patient with WS, expanding the spectrum of mutations in WS.
    Journal
    |
    WRN (WRN RecQ Like Helicase)
    |
    WRN mutation
    10ms
    Lynch-like syndrome with germline WRN mutation in Bulgarian patient with synchronous endometrial and ovarian cancer. (PubMed, Hered Cancer Clin Pract)
    The presented case contributes to the etiology of LLS and confirms the need for specific genetic testing, together with genetic counseling, in hereditary cancer syndromes. The use of combined information from clinicians, pathologists, genetic counselors, and data from NGS testing for cancer predisposition, clinical surveillance, and follow-up management in women with gynecology cancers, especially SEOC, could be improved.
    Journal
    |
    MLH1 (MutL homolog 1) • WRN (WRN RecQ Like Helicase)
    |
    WRN mutation
    10ms
    Clinical and genetic characteristics in pancreatic cancer from Chinese patients revealed by whole exome sequencing. (PubMed, Front Oncol)
    The TMB index was higher in patients with mutant-type KRAS MUT/TP53 MUT (p < 0.001), CDKN2A (p = 0.547), or SMAD4 (p = 0.064) compared to patients with wild-type KRAS/TP53, CDKN2A, or SMAD4. We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of the pancreas, which might have interesting implications for future individualized therapy and medication development.
    Journal • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • FGFR3 (Fibroblast growth factor receptor 3) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • GAS6 (Growth arrest specific 6) • MMP17 (Matrix Metallopeptidase 17) • WRN (WRN RecQ Like Helicase) • TENM4 (Teneurin Transmembrane Protein 4) • MMP7 (Matrix metallopeptidase 7) • USP7 (Ubiquitin Specific Peptidase 7)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • ATM mutation • PALB2 mutation • KRAS wild-type • RAS wild-type • SMAD4 mutation • FGFR3 fusion • WRN mutation
    1year
    Germline cancer gene expression quantitative trait loci are associated with local and global tumor mutations. (PubMed, Cancer Res)
    An EPHA5 eQTL was associated with mutations in cancer genes specific to colorectal cancer, and eQTL related to expression of APC, WRN, GLI1, FANCA, and TP53 were associated with mutations in genes specific to endometrial cancer. These findings provide evidence that germline-somatic associations are mediated through expression of specific cancer genes, opening new avenues for research on the underlying biological processes.
    Journal • Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • FANCA (FA Complementation Group A) • GLI1 (GLI Family Zinc Finger 1) • WRN (WRN RecQ Like Helicase) • EPHA5 (EPH Receptor A5) • GLI2 (GLI Family Zinc Finger 2)
    |
    ATM mutation • FANCA mutation • TP53 expression • WRN mutation • ATM expression • WRN expression
    over1year
    Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=146, Recruiting, Georgetown University | Trial completion date: Aug 2023 --> Jul 2025 | Trial primary completion date: Aug 2023 --> Jul 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    BARD1 mutation • WRN mutation
    |
    carboplatin • Zejula (niraparib)
    over1year
    A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) (clinicaltrials.gov)
    P2, N=35, Completed, University of Florida | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Aug 2022 | Trial primary completion date: Dec 2022 --> Aug 2022
    Trial completion • Trial completion date • Trial primary completion date
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDK2 (Cyclin-dependent kinase 2) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • BACH1 (BTB Domain And CNC Homolog 1) • FANCG (FA Complementation Group G) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FEN1 (Flap Structure-Specific Endonuclease 1) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    BARD1 mutation • WRN mutation • RPA1 mutation
    |
    Zejula (niraparib)
    over1year
    Sensitivities and Dependencies of BRAF Mutant Colorectal Cancer Cell Lines with or without PIK3CA Mutations for Discovery of Vulnerabilities with Therapeutic Potential. (PubMed, Medicina (Kaunas))
    Colorectal cancer cell lines bearing the frequent BRAF and PIK3CA mutations present many alterations of the parental cancer tissue. Described vulnerabilities represent leads for therapeutic exploration in colorectal cancers with the corresponding alterations.
    Preclinical • Journal
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • APC (APC Regulator Of WNT Signaling Pathway) • WRN (WRN RecQ Like Helicase)
    |
    TP53 mutation • BRAF V600E • BRAF mutation • PIK3CA mutation • BRAF V600 • APC mutation • WRN mutation
    over1year
    Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=146, Recruiting, Georgetown University | Trial completion date: Aug 2022 --> Aug 2023 | Trial primary completion date: Aug 2022 --> Aug 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    BARD1 mutation • WRN mutation
    |
    carboplatin • Zejula (niraparib)
    almost2years
    RecQ Helicase Somatic Alterations in Cancer. (PubMed, Front Mol Biosci)
    Downregulation of these proteins may allow for increased sensitivity to chemotherapy, and, therefore, may be important therapeutic targets. Here we provide a comprehensive review of our current understanding of the role of RecQ DNA helicases in cancer and discuss the potential therapeutic opportunities in targeting these helicases.
    Review • Journal
    |
    WRN (WRN RecQ Like Helicase) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4)
    |
    BLM mutation • WRN mutation • RECQL4 mutation
    almost2years
    Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer. (PubMed, Aging Cell)
    In correlation with patient data and above results, the TOP1 inhibitor-based targeted therapy showed that WRN-deficient melanoma tumors were highly sensitive to TOP1 inhibition in preclinical in vivo mouse model. Collectively, our findings identify hitherto unknown non-enzymatic role of WRN RECQL helicase in pathological mechanisms underlying TOP1cc processing and subsequent NF-κB-activation, offering a potential targeted therapy for WRN-deficient cancer patients.
    Journal
    |
    CHEK1 (Checkpoint kinase 1) • WRN (WRN RecQ Like Helicase) • NFKBIA (NFKB Inhibitor Alpha 2) • RECQL (RecQ Like Helicase) • RELA (RELA Proto-Oncogene)
    |
    WRN mutation • RECQL mutation
    almost2years
    High prevalence of myeloid malignancies in progeria with Werner syndrome is associated with p53 insufficiency. (PubMed, Exp Hematol)
    These results indicate that WS hematopoietic stem cells with WRN insufficiency acquire competitive fitness by inactivating p53, which may cause complex chromosomal abnormalities and the subsequent development of myeloid malignancies. These findings promote our understanding of the pathogenesis of myeloid malignancies associated with progeria.
    Journal
    |
    TP53 (Tumor protein P53) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • WRN (WRN RecQ Like Helicase)
    |
    TP53 mutation • PPM1D mutation • WRN mutation
    2years
    Pan-cancer analysis revealed characteristics of reversion mutations in homologous recombination repair genes (AACR 2022)
    This study analyzed clinical and mutational characteristics of reversion mutations in HRR genes, which could occur as single or multiple variants to restore the function of predisposed pathogenic HRR mutations, resulting in resistance to platinum-based chemotherapies or PARP inhibitors. Monitoring these mutations with tissue or liquid biopsy samples are crucial for treatment guidance.
    BRCA Biomarker • PARP Biomarker • Pan tumor
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • WRN (WRN RecQ Like Helicase) • FANCI (FA Complementation Group I) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation • WRN mutation • FANCI mutation • CHEK1 expression
    over2years
    Prognostic Implications of Six Altered Genes in Asian Non-Surgical Esophageal Carcinoma Patients Treated with Chemoradiotherapy. (PubMed, Onco Targets Ther)
    A Cox proportional hazard model based on the six prognosis-related genes was constructed and showed the ability in distinguishing EC patients with poorer disease outcomes in AEC and two validation cohorts. Six gene alterations were found to be potential unfavorable prognostic markers that might provide guidance in the treatment management for EC patients.
    Clinical • Journal
    |
    TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • FGF19 (Fibroblast growth factor 19) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • YAP1 (Yes associated protein 1) • WRN (WRN RecQ Like Helicase)
    |
    MYC amplification • BAP1 mutation • CCND1 amplification • BRIP1 mutation • WRN mutation
    over2years
    A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, University of Florida | Suspended --> Active, not recruiting | N=57 --> 35
    Enrollment closed • Enrollment change
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDK2 (Cyclin-dependent kinase 2) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • BACH1 (BTB Domain And CNC Homolog 1) • FANCG (FA Complementation Group G) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FEN1 (Flap Structure-Specific Endonuclease 1) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    BARD1 mutation • WRN mutation • RPA1 mutation
    |
    Zejula (niraparib)
    over2years
    A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) (clinicaltrials.gov)
    P2, N=57, Suspended, University of Florida | Recruiting --> Suspended
    Trial suspension
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDK2 (Cyclin-dependent kinase 2) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • BACH1 (BTB Domain And CNC Homolog 1) • FANCG (FA Complementation Group G) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FEN1 (Flap Structure-Specific Endonuclease 1)
    |
    BARD1 mutation • WRN mutation • RPA1 mutation
    |
    Zejula (niraparib)
    over2years
    Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=146, Recruiting, Georgetown University | Trial primary completion date: Jul 2021 --> Aug 2022
    Clinical • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
    |
    BARD1 mutation • WRN mutation
    |
    carboplatin • Zejula (niraparib)
    over2years
    A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) (clinicaltrials.gov)
    P2, N=47, Recruiting, University of Florida | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2022
    Trial completion date • Trial primary completion date
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDK2 (Cyclin-dependent kinase 2) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • BACH1 (BTB Domain And CNC Homolog 1) • FANCG (FA Complementation Group G) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FEN1 (Flap Structure-Specific Endonuclease 1)
    |
    BARD1 mutation • WRN mutation • RPA1 mutation
    |
    Zejula (niraparib)
    almost3years
    A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) (clinicaltrials.gov)
    P2, N=47, Recruiting, University of Florida | Suspended --> Recruiting
    Enrollment open
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDK2 (Cyclin-dependent kinase 2) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • BACH1 (BTB Domain And CNC Homolog 1) • FANCG (FA Complementation Group G) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
    |
    BARD1 mutation • WRN mutation • RPA1 mutation
    |
    Zejula (niraparib)
    almost3years
    A Trial of Niraparib in BAP1 and Other DNA Damage Response (DDR) Deficient Neoplasms (UF-STO-ETI-001) (clinicaltrials.gov)
    P2, N=47, Suspended, University of Florida | Recruiting --> Suspended
    Trial suspension
    |
    PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDK2 (Cyclin-dependent kinase 2) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • BACH1 (BTB Domain And CNC Homolog 1) • FANCG (FA Complementation Group G) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
    |
    BARD1 mutation • WRN mutation • RPA1 mutation
    |
    Zejula (niraparib)
    3years
    Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1, N=146, Recruiting, Georgetown University | Trial primary completion date: Jul 2020 --> Jul 2021
    Clinical • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
    |
    BARD1 mutation • WRN mutation
    |
    carboplatin • Zejula (niraparib)
    3years
    SUKSES-B: Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations (clinicaltrials.gov)
    P2, N=15, Completed, Samsung Medical Center | Recruiting --> Completed | N=28 --> 15 | Trial completion date: Sep 2021 --> Jan 2021 | Trial primary completion date: Sep 2021 --> Jan 2021
    Clinical • Trial completion • Enrollment change • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
    |
    BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • MRE11A mutation • RAD54L mutation • NBN mutation • WRN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation • RPA1 mutation
    |
    Lynparza (olaparib)
    over3years
    RECQ DNA Helicases and Osteosarcoma. (PubMed, Adv Exp Med Biol)
    This chapter will focus primarily on the known cellular functions of RECQL4 and how these may relate to tumorigenesis, as well as ongoing efforts to understand RECQL4's functions in vivo using animal models. Understanding the RECQ pathways will provide insight into avenues for novel cancer therapies in the future.
    Journal
    |
    BLM (BLM RecQ Like Helicase) • WRN (WRN RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4)
    |
    BLM mutation • WRN mutation • RECQL4 mutation
    over3years
    Prostatic carcinoma with neuroendocrine differentiation harboring the EWSR1-FEV fusion transcript in a man with the WRN G327X germline mutation: A new variant of prostatic carcinoma or a member of the Ewing sarcoma family of tumors? (PubMed, Pathol Res Pract)
    The WRN protein along with ATM, BRCA1, BRCA2, and RAD51 among others, comprise a DNA repair system by homologous recombination, and its alterations are associated with forms of hereditary PCa. We dispute whether the detection of EWSR1-FEV mandates one to diagnose the patient's tumor as a member of the Ewing sarcoma family.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • EWSR1 (EWS RNA Binding Protein 1) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2) • WRN (WRN RecQ Like Helicase)
    |
    BRCA1 mutation • ATM mutation • TMPRSS2-ERG fusion • WRN mutation
    |
    finasteride
    over3years
    [VIRTUAL] Prognostic significance of Werner syndrome protein in BRCA-mutated breast cancers (NCRI 2020)
    Conclusion Low WRN protein expression is associated with poor BCSS in patients with BRCA-mutated breast cancer. Impact statement Further understanding of the functional interaction between WRN and PARP1 in BRCA-mutated tumours may lead to novel therapeutic approaches which can be used to optimise the risk stratification for personalised treatment.
    BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • WRN (WRN RecQ Like Helicase)
    |
    BRCA2 mutation • BRCA1 mutation • BRCA mutation • WRN mutation
    almost4years
    WRN-Mutated Colorectal Cancer Is Characterized by a Distinct Genetic Phenotype. (PubMed, Cancers (Basel))
    A high prevalence of MSI-H/dMMR, higher TMB and PD-L1 in WRN-mut tumors were observed. Our data might serve as an additional selection tool for trials testing immune checkpoint antibodies in WRN-mut CRC.
    Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • WRN (WRN RecQ Like Helicase)
    |
    MSI-H/dMMR • WRN mutation
    almost4years
    [VIRTUAL] Genomic analysis of advanced malignant soft tissue tumors to suggest effect of genome-wide loss-of-heterozygosity of germline mutations/variants on anti-PD-1 immunotherapy response and survival of the patients. (ASCO 2020)
    Case 1 with pleural dissemination was treated with 5 cycles of Pembrolizumab (200mg/body, d1 q3weeks) but was progressive disease, while case 2 had no evaluable lesion after surgical removal of bone metastasis... Our results, for the first time, suggest that in malignant soft tissue tumors, accumulation of genome-wide LOH of germline mutations/variants, from which self-antigens could be generated, may influence tumor immune microenvironment, and thus influence immunotherapy response and survival of the patients. Research Funding: Japan Sarcoma Association Fund for Promotion of Genomic Medicine of Rare Cancers, The Osaka Foundation for The Prevention of Cancer and Lifestyle -related Diseases Research Grant
    Clinical • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    CD8 (cluster of differentiation 8) • MSH2 (MutS Homolog 2) • WRN (WRN RecQ Like Helicase)
    |
    MSH2 mutation • WRN mutation
    |
    Keytruda (pembrolizumab)