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    GENE:

    FANCM (FA Complementation Group M)

    i
    Other names: FANCM, FA Complementation Group M, KIAA1596, Fanconi Anemia-Associated Polypeptide Of 250 KDa, Fanconi Anemia Complementation Group M, ATP-Dependent RNA Helicase FANCM, Fanconi Anemia Group M Protein, Protein Hef Ortholog, FAAP250, Protein FACM, SPGF28, POF15
    3d
    RAD51C-XRCC3 complex regulates FANCM-mediated R-loop resolution to safeguard genome integrity. (PubMed, Sci Adv)
    The CX3 complex-mediated R-loop resolution is independent of its fork maintenance function. Collectively, we demonstrate a previously unidentified role of the CX3 complex in preventing R-loop-induced genome instability by regulating FANCM-mediated R-loop resolution.
    Journal
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    RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • FANCM (FA Complementation Group M) • XRCC3 (X-Ray Repair Cross Complementing 3)
    1m
    Fluzoparib as Adjuvant Treatment in Patients With Germline Homologous Recombination Repair (HRR) Mutated Primary Breast Cancer (Flamenco) (clinicaltrials.gov)
    P2, N=334, Not yet recruiting, Fudan University
    New P2 trial • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCM (FA Complementation Group M) • RAD52 (RAD52 Homolog DNA Repair Protein) • RPA1 (Replication Protein A1) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
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    HER-2 negative • PALB2 mutation • PGR positive • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation
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    capecitabine • AiRuiYi (fluzoparib)
    1m
    The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts. (PubMed, Nucleic Acids Res)
    These studies underscore the role of SMC5/6 in sensing TRCs and define the SMC5/6-BTRR-FANCM-FANCD2 axis as an important player in mitigating TRC-induced genome instability. Our findings also provide therapeutic opportunities for targeting this axis for effective treatment of SETX-deficient tumors.
    Journal
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    FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2)
    2ms
    Characteristics of uterine leiomyosarcoma: a clinicopathological and molecular genetic analysis of twenty-four cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
    Secondary morphological changes in uterine leiomyosarcomas associated with hormone therapy pose significant diagnostic challenges. Next generation sequencing can provide valuable evidence for the diagnosis of morphologically challenging cases of leiomyosarcoma in clinical practice.
    Retrospective data • Journal • Tumor mutational burden • BRCA Biomarker
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • FANCE (FA Complementation Group E)
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    TP53 mutation • TMB-H • TMB-L • RAD51B mutation
    2ms
    TBCRC 048: Olaparib In Metastatic Breast Cancer (clinicaltrials.gov)
    P2, N=114, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Dec 2025 --> Jun 2026
    Trial completion date
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    PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
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    HR positive • PALB2 mutation • PGR positive • BRCA mutation
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    Lynparza (olaparib)
    2ms
    CHAMP1 complex promotes heterochromatin assembly and reduces replication stress. (PubMed, Proc Natl Acad Sci U S A)
    Notably, CHAMP1 deficiency induces synthetic lethality with FANCM inhibition in ALT-positive tumor cells, and the CHAMP1 complex is essential for the survival of CCNE1-amplified ovarian cancers. These findings uncover a heterochromatin-based mechanism of replication fork stabilization and suggest that CHAMP1 may represent a candidate therapeutic vulnerability in cancers with elevated RS.
    Journal
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    CCNE1 (Cyclin E1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • FANCM (FA Complementation Group M) • SETDB1 (SET Domain Bifurcated Histone Lysine Methyltransferase 1)
    2ms
    Complex Relationships Between Homologous Recombination Deficiency (HRD) Score and Mutational Status of Homologous Recombination Repair (HRR) Genes in Prostate Carcinomas. (PubMed, Int J Mol Sci)
    The majority of CDK12-mutated tumors exhibited a distinct type of copy number variations (CNV)-a tandem duplication phenotype. Our study suggests that the selection of PC patients for PARPi treatment requires a significant revision of existing attitudes towards tumor genetic profiling.
    Journal • BRCA Biomarker • PARP Biomarker
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    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) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCM (FA Complementation Group M)
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    HRD • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation
    3ms
    TSN Disrupts Fanconi Anemia Pathway Activation Through JAK/STAT1-Mediated Transcriptional Repression of FA Core Subunits in Bladder Cancer. (PubMed, Dose Response)
    TSN selectively sensitized bladder cancer cells to UVC-induced cytotoxicity (IC50 decreased 35%, P = 0.026, n = 3), without affecting the viability of human urothelial cell SV-HUC-1 cells or lung adenocarcinoma A549 cells (both P > 0.05, n = 3). TSN inhibits FA DNA repair signaling in bladder cancer by suppressing JAK/STAT1-mediated FA core gene transcription, supporting its potential as a combinatorial agent to overcome cisplatin resistance.
    Journal
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    FANCA (FA Complementation Group A) • FANCF (FA complementation group F) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • STAT1 (Signal Transducer And Activator Of Transcription 1) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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    cisplatin
    3ms
    Cell-Active Peptide Inhibitors of the FANCM-RMI Interaction. (PubMed, J Med Chem)
    Conjugation to a cell-penetrating peptide resulted in inhibitors that induced an antiproliferative effect in ALT-positive osteosarcoma cell lines. These inhibitors represent the first bioactive RMI binders that can be used as chemical tools for studying the involvement of FANCM-RMI in ALT-driven cancers.
    Journal
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    FANCM (FA Complementation Group M)
    3ms
    Large-scale meta-analysis and precision functional assays identify FANCM regions in which PTVs confer different risks for ER-negative and triple-negative breast cancer. (PubMed, Breast)
    Importantly, our results confirm previous data indicating that p.Arg658∗ carriers are at moderate risk of developing ER-neg (OR = 2.08, P = 0.030) and TN (OR = 3.26; P = 0.0034), whereas carriers of p.Gln1701∗ and p.Gly1906Alafs∗12 should not be considered at increased risk. Our data are useful for counseling carriers of FANCM PTVs, but further analyses are warranted to obtain more precise risk estimates.
    Retrospective data • Journal
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    ER (Estrogen receptor) • FANCM (FA Complementation Group M)
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    ER negative
    5ms
    Association of Genetic Risk Variants in SETBP1, FANCM, and LSP1 with Familial Breast Cancer in the Pakistani Pashtun Population. (PubMed, Pak J Med Sci)
    This research enhances our understanding of the genetic risk factors for breast cancer in the Pashtun population and underscores the potential importance of the SETBP1 rs11082414 variant in identifying individuals at risk. The identification of genetic biomarkers can facilitate the development of targeted drug therapies, improve early detection, and enhance the effective management of breast cancer.
    Journal
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    SETBP1 (SET Binding Protein 1) • FANCM (FA Complementation Group M)
    5ms
    The TONSL-MMS22L complex and FANCM form an interdependent complex on chromatin to counter replication stress. (PubMed, bioRxiv)
    Cancer patients with tumors with wildtype FANCM and low expression of TONSL-MMS22L have a more favorable prognosis than those with high expression. Thus, FANCM-TONSL-MMS22L acts coordinately as a complex on chromatin that resolves replication stress, and this complex may present a therapeutic target for wildtype FANCM-linked cancer.
    Journal
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    RAD51 (RAD51 Homolog A) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2)