Molecular Mediator of Prostate Cancer Progression and Its Implication in Therapy
Surinder K. Batra, Moorthy P. Ponnusamy in Gene Regulation and Therapeutics for Cancer, 2021
TCGA database suggested mutations in many DNA repair genes like BRCA1, BRCA2, FANCD2, CKD12 and ATM in primary prostate cancer, although it is to be noted that the frequency of DNA repair mutations in localized prostate cancer is low [108, 178, 179]. Interestingly, mutations in DNA repair enzymes (BRCA2, ATM, BRCA1, FANCA, RAD51B, RAD51C, MLH1, and MSH2) are the major disease-specific mutations in mCRPC [180, 181]. The understanding that a quarter of men with mCRPC have mutations in DNA repair pathway genes such as BRCA genes has led to clinical trials with poly ADP ribose polymerase (PARP) inhibitors. PARPs are required to repair the DNA single-strand breaks through base-excision repair. It has been shown that cancer cells with BRCA gene mutations become significantly more sensitive to PARP inhibitors as a therapeutic approach popularly known as synthetic lethal strategy [180, 181]. It is further noted that mutations of other DNA repair pathway genes can be sensitive to PARP inhibitors. These genes are ATM, BRIP1, BARD1, CDK12, CHEK2, FANCA, NBN, PALB2, and RAD51 [182, 183].
Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow in Fetal and Perinatal Skeletal Dysplasias, 2012
Genetics: a genetically heterogeneous disorder, 13 genes have been identified to date, which define the respective FA complementation groups: FANCA (includes the previously designated FANCH), FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG (XRCC9), FANCI (KIAA1794), FANCJ (BRIP1), FANCL (PHF9), FANCM, FANCN ( PALB2), and FANCO ( RAD51C). All the FA subtypes are autosomal recessive disorders, except for FANCB which is X-linked. The products of the genes FANC- A, C, E, F, G, L are part of a nuclear complex which regulate the monoubiquitination of FANCD2 during the S phase of the cell cycle or after DNA damage by crosslinking agents (e.g. mitomycin C, diepoxybutane (DEB), cisplatin), which targets FANCD2 to BRCA1 nuclear foci containing BRCA2 (FANCD1) and RAD51. The FA/BRCA pathway (FANCD1-BRCA2, FANCJ-BRIP1, FANCN-PALB2) is implicated in the repair of DNA damage. The diagnosis first relies on the finding of increased chromosomal breakage or rearrangements when a patient’s cell culture is exposed to diepoxybutane (DEB) or radial figures when exposed to mitomycin C (MMC).
Overview of Traditional Methods of Diagnosis and Treatment for Women-Associated Cancers
Shazia Rashid, Ankur Saxena, Sabia Rashid in Latest Advances in Diagnosis and Treatment of Women-Associated Cancers, 2022
Ovarian cancer refers to any cancerous growth that originates in the ovaries, or in related areas of the fallopian tube and the peritoneum. The cause of ovarian cancer is multifactorial which mainly include genetic, immunologic, and environmental factors. Some most common causes of ovarian cancer are inherited gene changes (including BRCA1, BRCA2, BRIP1, RAD51C, RAD51D and genes associated with Lynch syndrome), postmenopausal hormone replacement therapy and endometriosis [16]. The use of oral contraceptives, like birth control pills, has been shown to dramatically reduce the risk of ovarian cancer and endometrial cancer [17].
Curcumin induces DNA damage by mediating homologous recombination mechanism in triple negative breast cancer
Published in Nutrition and Cancer, 2020
Gamze Guney Eskiler, Elvan Sahin, Asuman Deveci Ozkan, Ozlem Tugce Cilingir Kaya, Suleyman Kaleli
DNA damage response is regulated by different pathways including base excision repair (BER), mismatch repair (MMR), non-homologous end joining (NHEJ) and homologous recombination (HR)-associated genes such as BRCA1/2, RAD50/51, PALB2, CHEK2, BARD1, BRIP1 etc. The BRCA1 gene plays a crucial role in HR mechanism in response to DNA double-strand breaks (dsDNA). BRCA1 interacts with RAD51 to repair dsDNA breaks and maintain genomic stability and thus, BRCA1 and RAD51 are the main mediator of HR mechanism (9–12). Furthermore, phosphorylation of H2AX (γH2AX) is an important step in recruitment of DNA repair proteins and thus, BRCA1, RAD50, and NBS1 localize with γ-H2AX at sites of DNA damage (13,14). Additionally, DNA breaks are also recognized by poly (ADP-ribose) polymerase 1 (PARP1) and thus PARP1 mediates both DNA repair and cell death (15,16). Therefore, the association H2AX, PARP1, BRCA1, and RAD51 with DNA repair and DNA-damage-induced cell death should be further elucidated.
Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: a two-stage association study and functional investigation
Published in OncoImmunology, 2019
Lei Fan, Peng Zhou, Qi Hong, Ao-Xiang Chen, Guang-Yu Liu, Ke-Da Yu, Zhi-Ming Shao
Breast cancer appears to be a consequence of both genetic and environmental influences. In linkage analysis and association studies, several susceptibility loci and genes, including BRCA1, BRCA2, ATM and TP53, have been identified as the causal factors of inherited predisposition to breast cancer25,26 Considering the close functional relationships between both PALB2 and BRCA2 and BRIP1 and BRCA1, it is conceivable that mutations and polymorphisms in PALB2 and BRIP1 may account for a proportion of BRCA1/BRCA2-negative breast cancers27,28 Despite these significant advances, the identified genes and loci have failed to satisfactorily explain rates of inheritance. For most familial as well as sporadic cases, a substantial component of risk may be multiple low-penetrance genes29 Recently, large-scale genome-wide association studies identified several new, independent, low-penetrance susceptibility loci that are strongly associated with breast cancer in populations of diverse ethnicity30,31 Although whole-genome screening of cancer susceptibility loci is an available methodology, the classic candidate gene strategy of investigating carcinogenesis-related pathways is still frequently employed.
Breast cancer glycan biomarkers: their link to tumour cell metabolism and their perspectives in clinical practice
Published in Expert Review of Proteomics, 2021
Tomas Bertok, Veronika Pinkova Gajdosova, Aniko Bertokova, Natalia Svecova, Peter Kasak, Jan Tkac
Genetic predispositions to BCa significantly affect not only screening but also follow-up recommendations. Patients with a family history very often exhibit a mutation in genes such as BRCA1, BRCA2, PTEN (85% lifetime risk), PT53, CDH1 and STK1 (highly penetrant) or CHEK2, BRIP1, ATM and PALB2 (moderately penetrant) genes [22]. However, magnetic resonance-imaging is still the most sensitive and accessible procedure used for BCa diagnostics. Similarly to prostate’s MRI PI-RADS system, BI-RADS is being used as a tool to make a decision as to whether to proceed further with a breast biopsy (with BI-RADS 3 and above, biopsy is usually considered, with 5 being the highest score). For different results of biopsy concordant/discordant benign/malignant (i.e. depending on whether the lesion is thought to be benign/malignant prior to the core needle biopsy result), different follow-ups (short-term or annual) are usually needed [23]. If biochemical markers are used for the diagnostics/prognostics of BCa, very often a multiplexed format of analysis is required [24], like one recently published, to achieve high assay accuracy [25].
Related Knowledge Centers
- DNA Damage
- DNA Replication
- Excitotoxicity
- Helicase
- Homologous Recombination
- Oxidative Stress
- Protein
- Gene
- Mitochondrion
- Neuron