- •Deficiency of CHEK1, FANCM and TP53I3 led to reduced homologous recombination repair efficiency.
- •Deficiency of RAD1, CHEK1 or FANCM led to a decrease in cellular viability.
- •Deficiency of CHEK1, RAD1 or TP53I3 displayed increased sensitivity to cisplatin.
- •Deficiency of CHEK1, REC8 or RAD1 display increased sensitivity etoposide.
- •Results corroborate whole exome sequencing and bioinformatics analyses that identified FANCM, RAD1, CHEK1 and TP53I3, as putative germline risk loci in inherited breast and ovarian cancer risk.
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
- GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.Nat Genet. 2013; 45: 362-370
- Finding the missing heritability of complex diseases.Nature. 2009; 461: 747-753
- Whole exome sequencing: a necessary tool for the future of clinical cancer care.J Cancer Biol Res. 2017; 5
- Reanalysis of BRCA1/2 negative high risk ovarian cancer patients reveals novel germline risk loci and insights into missing heritability.PLoS One. 2017; 12e0178450
- Fancm-deficient mice reveal unique features of Fanconi anemia complementation group M.Hum Mol Genet. 2009; 18: 3484-3495
- Chk1 is haploinsufficient for multiple functions critical to tumor suppression.Cancer Cell. 2004; 6: 45-59
- A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice.Nat Genet. 2007; 39: 93-98
- Mouse Rad1 deletion enhances susceptibility for skin tumor development.Mol Cancer. 2010; 9: 67
- Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis.Dev Cell. 2005; 8: 949-961
- Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.PLoS Biol. 2011; 9: 1-18
- Identifying the effects of BRCA1 mutations on homologous recombination using cells that express endogenous wild-type BRCA1.J Vis Exp. 2011; 48: 3-7
- Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing.Hum Mutat. 2013; 34: 439-445
- XRCC3 promotes homology-directed repair of DNA damage in mammalian cells.Genes Dev. 1999; 13: 2633-2638
- Statistical notes for clinical researchers: assessing normal distribution (2) using skewness and kurtosis.Restor Dent Endod. 2013; 38: 52
- Loss of heterozygosity: what is it good for?.BMC Med Genom. 2015; 8: 1-12
- Genes essential for cell viability that are linked to tumor suppressor genes play a role in cancer susceptibility.Cell Cycle. 2010; 9: 3144-3145
- Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas.Clini Cancer Res. 2014; 20: 764-775
- BRCA1- and BRCA2-deficient cells are sensitive to etoposide-induced DNA double-strand breaks via topoisomerase II.Cancer Res. 2007; 67: 7078-7081
- Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.Nature. 2005; 434: 917-921
- Etoposide pathway.Pharmacogenet Genom. 2009; 19: 552-553
- Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase.Nature. 2005; 434: 913-917
- Olaparib for metastatic breast cancer in patients with a germline BRCA mutation.N Engl J Med. 2017; 377: 523-533
- PARP inhibitors in ovarian cancer.Ann Oncol. 2016; 27 (no. December): i40-i44
- PARP inhibitors in ovarian cancer: evidence, experience and clinical potential.Ther Adv Med Oncol. 2017; 9: 253-267
- FDA approval summary: olaparib monotherapy in patients with deleterious germline BRCA-mutated advanced ovarian cancer treated with three or more lines of chemotherapy.Clin Cancer Res. 2015; 21: 4257-4261
- Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation.J Clin Oncol. 2015; 33: 244-250
- FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.Hum Mol Genet. 2015; 24: 5345-5355
- Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene.Oncotarget. 2017; 8: 50930-50940
- Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint.Genes Dev. 2000; 14: 1448-1459
- Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response.Br J Cancer. 2015; 112: 901-911
- Detection of CHK1 and CCND1 gene copy number changes in breast cancer with dual-colour fluorescence in-situ hybridization.Histopathology. 2011; 58: 601-607
- Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences.Mol Cell Biol. 2003; 23: 8820-8828
- BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner.Oncotarget. 2015; 6: 7606-7618
- REC8 functions as a tumor suppressor and is epigenetically downregulated in gastric cancer, especially in EBV-positive subtype.Oncogene. 2017; 36: 182-193
- REC8 is a novel tumor suppressor gene epigenetically robustly targeted by the PI3K pathway in thyroid cancer.Oncotarget. 2015; 6: 39211-39224