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CHEK2 (Checkpoint kinase 2)
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19h
Lipid metabolism associated PLPP4 gene drives oncogenic and adipogenic potential in breast cancer cells. (PubMed, Biochim Biophys Acta Mol Cell Biol Lipids)
All these findings together, for first time, demonstrated that BMP2 drives PLPP4 to enhance both oncogenic and adipogenic potential in breast cancer cells. This article uncovers the perturbed lipid metabolism associated PLPP4 acts as oncogene presumably by modulating adipogenic activity in cancer cells.
Journal
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CHEK2 (Checkpoint kinase 2) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • LEP (Leptin) • LPCAT1 (Lysophosphatidylcholine Acyltransferase 1) • BMP2 (Bone Morphogenetic Protein 2)
3d
Genomic profiling of aggressive pathologic features in lung adenocarcinoma. (PubMed, Lung Cancer)
This analysis demonstrated the correlation of pathologic features with common driver mutations, key mutations and canonical oncogenic signaling pathways. The data highlighted the similarities and differences among these features horizontally, and provide new insights in TNMB classification and prognostic assessment.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • TOP2A (DNA topoisomerase 2-alpha) • LRP1B (LDL Receptor Related Protein 1B) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CHEK2 (Checkpoint kinase 2)
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TP53 mutation • BRAF V600E • BRAF V600 • PTEN mutation • STK11 mutation • CHEK2 mutation
3d
Germinal pathogenic CHEK2, novel APC and somatic JAK2V617F variants in a young patient with colorectal cancer, atypical leukemia, cerebral tumour and aggressive course. (PubMed, Ecancermedicalscience)
In this report, we present the clinical case of a 35-year-old patient exhibiting multiple tumours, an aggressive course, whose genetic analysis revealed a germinal mutation in CHEK2 gen, somatic JAK2V617F and a germinal novel variant in Adenomatous Polyposis Coli (APC) gene of uncertain significance may account for the polyposis and medulloblastoma in the patient, given the variant's genomic location. It is also possible that two germline mutations (CHEK2 and APC) are causing two concurrent conditions in the patient with poorer clinical course.
Journal
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JAK2 (Janus kinase 2) • APC (APC Regulator Of WNT Signaling Pathway) • CHEK2 (Checkpoint kinase 2)
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CHEK2 mutation
4d
The breast tumor immune microenvironment of DNA double-strand break repair pathogenic variant carriers is enriched with tumor-associated macrophages. (PubMed, Cancer Epidemiol Biomarkers Prev)
These results support further characterization of macrophage characteristics and abundance in the breast tumor microenvironment of DSB repair-related pathogenic variant carriers.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCM (FA Complementation Group M) • STAT1 (Signal Transducer And Activator Of Transcription 1) • RECQL (RecQ Like Helicase) • FANCC (FA Complementation Group C)
6d
Targeting CHEK2-YBX1&YBX3 regulatory hub to potentiate immune checkpoint blockade response in gliomas. (PubMed, bioRxiv)
Collectively, these findings reveal an immunosuppressive mechanism mediated by the CHK2-YBX1&YBX3 hub proteins. Therefore, CHK2-YBX1&YBX3 hub targeting in combination with immune checkpoint blockade therapies in gliomas is warranted.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • CHEK2 (Checkpoint kinase 2) • YBX1 (Y-Box Binding Protein 1)
7d
LDHB silencing enhances the effects of radiotherapy by impairing nucleotide metabolism and promoting persistent DNA damage. (PubMed, Sci Rep)
Nucleotide supplementation partially attenuated DNA damage caused by combined LDHB silencing and radiotherapy. These findings suggest that LDHB supports metabolic homeostasis and DNA damage repair in NSCLC, while its silencing enhances the effects of radiotherapy by impairing nucleotide metabolism and promoting persistent DNA damage.
Journal
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TP53 (Tumor protein P53) • LDHB (L-lactate dehydrogenase B chain) • CHEK2 (Checkpoint kinase 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
8d
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
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HER-2 negative
10d
Association of a CHEK2 somatic variant with tumor microenvironment calprotectin expression predicts platinum resistance in a small cohort of ovarian carcinoma. (PubMed, PLoS One)
Also, PD-L2 levels were significantly higher in PR patients positive for this CHEK2 variant (p = 0.048), underscoring the need to explore its potential therapeutic role for this cancer. Our results suggest an interplay between TME and DNA repair variants that results in a multifactorial nature of HGSOC resistance to platinum chemotherapy.
Journal
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CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2)
10d
Primordial follicle survival and changes in ovarian vasculature may be independently regulated during chemotherapy. (PubMed, Endocrinology)
In the current study, we investigated strategies to protect ovarian function from chemotherapy-induced toxicity by evaluating the effects of cisplatin, doxorubicin, or cyclophosphamide on ovarian vasculature and primordial follicle survival. Long-term ex vivo culture and in vivo experiments demonstrated the ability of ovarian vasculature to recover from cisplatin-induced damage. In conclusion, our study suggests that the ovarian follicle survival and vascular integrity may be independently regulated as independent processes, governed by distinct signaling pathway or mechanisms.
Journal
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CHEK2 (Checkpoint kinase 2) • CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
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cisplatin • doxorubicin hydrochloride • cyclophosphamide
14d
The Influence of Homologous Recombination Repair on Temozolomide Chemosensitivity in Gliomas. (PubMed, Carcinogenesis)
Noteworthy efforts have been directed towards exploring inhibitors of these pathways in recent research endeavors, culminating in encouraging outcomes. In conclusion, the involvement of HRR in glioma resistance unveils novel therapeutic avenues, with targeting crucial molecules in the HRR pathway, holding promise for enhancing the effectiveness of TMZ therapy.
Journal
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HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1)
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temozolomide
16d
Analysis of germline-somatic mutational connections in colorectal cancer reveals differential tumorigenic patterns and a novel predictive marker for germline mutation carriers. (PubMed, Cancer Lett)
Our findings elucidate different germline tumorigenic patterns not driven by deficient MMR. Somatic ERBB2 amplification in CRC can serve as an indicator for germline genetic testing when traditional risk features are absent.
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • KDM6A (Lysine Demethylase 6A)
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TP53 mutation • HER-2 amplification • ARID1A mutation
16d
Pathogenic role of CHEK2 variants in Hungarian cancer patients: implications for breast cancer risk and genetic counselling (PubMed, Magy Onkol)
Despite their frequent occurrence, lp-CHEK2 variants confer a negligible risk of breast cancer and show no association with other tumour types. Disease-causing CHEK2 variants, however, have implications for the clinical management of breast cancer patients according to current guidelines.
Journal
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CHEK2 (Checkpoint kinase 2)
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TruSight Hereditary Cancer Panel
16d
Effects of breast size on breast reconstruction in BRCA mutation carriers and genetic high-risk patients after bilateral mastectomy. (PubMed, Breast Cancer)
The preoperative breast size of gene mutation carriers influences the postmastectomy reconstructive choice. TMG and SGAP flaps are suitable options for bilateral reconstruction of genetic susceptible patients with small breasts, while DIEP flaps are preferred in larger breast sizes. With increasing breast size an elevated risk for elective revisions after either IBR or ABR need to be considered. Women with medium-to-large breasts exhibit increased morbidity related to expansion and genetic high-risk patients may benefit from prior reduction mammoplasty.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
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PALB2 mutation • BRCA mutation
17d
ADAM9 mediates Cisplatin resistance in gastric cancer cells through DNA damage response pathway. (PubMed, Med Oncol)
It is suggested that ADAM9 is involved in Cisplatin resistance in gastric cancer cells, and its mechanism is related to the activation of ATM-CHK2 pathway in DNA damage repair. These data demonstrate that ADAM9 plays a pro-cancer role and mediates Cisplatin resistance in gastric cancer, which may be a new target to overcome chemotherapy resistance.
Journal
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CHEK2 (Checkpoint kinase 2) • ADAM9 (ADAM Metallopeptidase Domain 9)
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cisplatin
20d
Pan-cancer genetic profiles of mitotic DNA integrity checkpoint protein kinases. (PubMed, Cancer Biomark)
However, further efforts are necessary to validate their clinical value for diagnosis and prognosis and to develop practical applications in clinical settings. Nevertheless, these pan-cancer profiles offer a better overall understanding as well as useful information for future reference regarding mitotic DNA integrity checkpoint signaling in cancer.
Journal • BRCA Biomarker • Pan tumor
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BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1) • CDK2 (Cyclin-dependent kinase 2) • CDK1 (Cyclin-dependent kinase 1) • NEK11 (NIMA Related Kinase 11) • PLK2 (Polo Like Kinase 2) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
24d
Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke. (PubMed, Int J Mol Sci)
Overall, our findings lend support to the existence of senescence after ischemic stroke in neurons and microglia/macrophages. However, there is still room to gain further insight into the role of senescence in the pathophysiology of ischemic stroke and in the implementation of successful senolytic therapy.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • IL1B (Interleukin 1, beta)
25d
ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2025 --> Mar 2027
Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • 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) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
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Lynparza (olaparib)
25d
Germline variants in CDKN2A wild-type melanoma prone families. (PubMed, Mol Oncol)
In particular, XPCL48F was found in 8 indexes; thus, the allele fraction (0.07) was significantly higher than in comparable healthy populations (0.02-0.03; P-values from 0.007 to 0.014). In conclusion, we found that several melanoma-prone families have pathogenic variants in genes not usually linked to melanoma.
Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MAP3K6 (Mitogen-Activated Protein Kinase Kinase Kinase 6)
25d
Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses. (PubMed, Nat Med)
We find that most female reproductive health diagnoses have a heritable component, with varying degrees of polygenicity and discoverability. Finally, we identify pleiotropic loci and genes that function in genital tract development (WNT4, PAX8, WT1, SALL1), hormonal regulation (FSHB, GREB1, BMPR1B, SYNE1/ESR1) and folliculogenesis (CHEK2), underlining their integral roles in female reproductive health.
Journal
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ER (Estrogen receptor) • WT1 (WT1 Transcription Factor) • CHEK2 (Checkpoint kinase 2) • PAX8 (Paired box 8) • SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1) • BMPR1B (Bone Morphogenetic Protein Receptor Type 1B)
25d
Pathogenic germline variants in cancer predisposition genes in patients with multiple primary cancers in an Asian population and the role of extended panel genetic testing. (PubMed, ESMO Open)
Patients with MPC were more likely to harbour a PGV. Extended testing improved PGV detection rates, particularly for less well-known cancer predisposition genes.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • TET2 (Tet Methylcytosine Dioxygenase 2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • BARD1 (BRCA1 Associated RING Domain 1) • DDX41 (DEAD-Box Helicase 41) • FANCL (FA Complementation Group L) • CTNNA1 (Catenin Alpha 1) • RECQL4( RecQ Like Helicase 4) • SPINK1 (Serine peptidase inhibitor, kazal type 1) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • TNFRSF13B (TNF Receptor Superfamily Member 13B)
27d
Replication stress: an early key event in ochratoxin a genotoxicity? (PubMed, Arch Toxicol)
However, OTA did not appear to efficiently activate ATR-Chk1 and ATM-Chk2 DNA damage response pathways, suggesting that cells with under-replicated DNA or unresolved DNA damage may escape checkpoint control and may continue into mitosis, with potentially deleterious consequences for genomic integrity. Overall, results from this study provide first experimental evidence for perturbation of the S phase replisome machinery by OTA and point toward replication stress as an early key event in OTA genotoxicity.
Journal
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CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
28d
ROS-ATM-CHK2 axis stabilizes HIF-1α and promotes tumor angiogenesis in hypoxic microenvironment. (PubMed, Oncogene)
Meanwhile, HIF-1α phosphorylation induced by CHK2 promotes complex formation between HIF-1-α and the deubiquitination enzyme USP7, increasing stability under hypoxic conditions. This novel modification of the crosstalk between phosphorylation and ubiquitination of HIF-1α mediated by CHK2 enriches the post-translational modification spectrum of HIF-1α, thus offering novel insights into potential anti-angiogenesis therapies.
Journal
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HIF1A (Hypoxia inducible factor 1, alpha subunit) • CHEK2 (Checkpoint kinase 2) • USP7 (Ubiquitin Specific Peptidase 7)
28d
Small molecule as potent hepatocellular carcinoma progression inhibitor through stabilizing G-quadruplex DNA to activate replication stress responded DNA damage. (PubMed, Chem Biol Interact)
In vivo studies further supported these findings. In summary, TA-1 is a potent VEGF G-quadruplex stabilizer that inhibits liver cancer progression.
Journal
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CHEK2 (Checkpoint kinase 2) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
28d
Discovery of 4-(2-(methylamino)thiazol-5-yl)pyrimidin-2-amine derivatives as novel cyclin-dependent kinase 12 (CDK12) inhibitors for the treatment of esophageal squamous cell carcinoma. (PubMed, Bioorg Chem)
In addition, H63 exhibited favorable pharmacokinetic properties, good safety, and prominent anti-ESCC activity in vivo. The present study suggests that CDK12 is a promising target for ESCC treatment, and H63 is a promising candidate for further clinical development as an anti-ESCC drug.
Journal
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CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
1m
Profiling genetic mutations in the DNA damage repair genes of oral squamous cell carcinoma patients from Pakistan. (PubMed, Sci Rep)
TP53p.P33R was predominantly associated with moderately differentiated tumors (84.60%), naswar users (86.60%) and positive family history of cancer (91.60%). The TP53p.P33R, ATRp.M211T and CHEK1p.I437V mutations were found recurrently in 21/27 (77.7%), 20/27 (74.04%), and 27/27 (100%) patients, suggesting its potential biomarker applications in local screening.
Journal
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TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
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TP53 mutation • ATM mutation • CHEK2 mutation • CHEK1 mutation
1m
Genetic Landscape of Mucosal Melanoma: Identifying Pathogenic Germline Variants. (PubMed, Pigment Cell Melanoma Res)
Our findings reveal a high prevalence (50%) of pathogenic germline variants among MM patients, with CHEK2 and APC variants identified in 12.5% of cases each, and individual variants detected in MUTYH, ATM, RB1, and RECQL4. These results suggest a germline-driven cancer susceptibility in MM, exceeding the 15% prevalence observed in cutaneous melanoma using the same inclusion criteria.
Journal
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RB1 (RB Transcriptional Corepressor 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog) • RECQL4( RecQ Like Helicase 4)
1m
Pathogenic germline variants in Chinese pancreatic adenocarcinoma patients. (PubMed, Nat Commun)
Using an integrative multi-omics and functional validation paradigm, we discover that deleterious variants of uncertain significance may compromise CFTR's tumor suppressor function, and demonstrate the clinical relevance by using patient derived organoids for drug screen. Our multifaceted approach not only deepens the knowledge of population differences in PAAD germline mutations but also unveils potential avenues for targeted therapeutic interventions.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERCC2 (Excision repair cross-complementation group 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51D (RAD51 paralog D) • GNAS (GNAS Complex Locus)
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ATM mutation • CHEK2 mutation • RAD51D mutation
1m
Reclassification of variants of uncertain significance by race, ethnicity, and ancestry for patients at risk for breast cancer. (PubMed, Front Oncol)
This study allows for improved and more equitable genetic counseling. It may also provide more reassurance to those groups that may have a higher likelihood of VUS results.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
1m
Dynamic Monitoring of Circulating Tumor DNA to Predict the Risk of Non In Situ Recurrence of Postoperative Glioma: A Prospective Cohort Study. (PubMed, Cancer Med)
In glioma patients undergoing primary surgery, dynamic monitoring of ctDNA and genotyping can be used for early risk stratification, efficacy monitoring, and early recurrence detection, and provide a basis for clinical research to evaluate early therapeutic intervention.
Journal • Circulating tumor DNA
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EGFR (Epidermal growth factor receptor) • NF1 (Neurofibromin 1) • MUC16 (Mucin 16, Cell Surface Associated) • CHEK2 (Checkpoint kinase 2)
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TP53 mutation • KRAS mutation • EGFR mutation • CHEK2 mutation
1m
Prevalence of Constitutional Pathogenic Variant in a Cohort of 348 Patients With Multiple Primary Cancer Addressed in Oncogenetic Consultation. (PubMed, Mol Genet Genomic Med)
Patients referred for oncogenetic testing with MPM are more likely to carry pathogenic variants in cancer predisposition genes than patients with a single primary cancer (p < 0.05), especially if the cancers are related to the same predisposition syndrome. If the cancers are unrelated, no statistical difference in comparison to the single-cancer population was observed. For these latter patients, we recommend using the specific criteria of each tumor to propose appropriate genetic testing.
Journal • BRCA Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
1m
Breast, Colorectal, and Pancreatic Cancer Mortality With Pathogenic Variants in ATM, CHEK2, or PALB2. (PubMed, J Clin Oncol)
Patients with ATM, CHEK2, or PALB2 PVs had similar breast, colorectal, and pancreatic cancer mortality to the average genetically tested patient with their cancer type.
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
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HER-2 positive • HER-2 negative • PGR positive • EGFR positive
1m
SPORE: A Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy (clinicaltrials.gov)
P2, N=63, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026
Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C)
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MSK-IMPACT
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Keytruda (pembrolizumab) • Lynparza (olaparib)
1m
Population-based study of recurrent DNA damage response gene variants in breast cancer cases. (PubMed, Breast Cancer Res Treat)
The studied DDR gene variants were present in 9% of the unselected cases. As the presence of germline pathogenic variants can provide additional value for surgical decision-making and affect the choice of oncological treatments, the results promote the benefits of genetic testing as a part of breast cancer diagnostics.
Journal • BRCA Biomarker
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ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • FANCM (FA Complementation Group M)
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ER positive
1m
Causative Genes of Homologous Recombination Deficiency (HRD)-Related Breast Cancer and Specific Strategies at Present. (PubMed, Curr Oncol)
Therefore, a large-scale database, including clinical information and a long-term follow-up should be established, after which a periodical assessment is mandatory. The clinical behavior of each gene should be clarified based on a large-scale database, or, in other words, real-world data.
Review • Journal • BRCA Biomarker • PARP Biomarker
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ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BARD1 (BRCA1 Associated RING Domain 1)
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HRD • BRCA mutation
1m
Considerations for hereditary breast and ovarian cancer syndrome molecular diagnosis: experience from the clinical practice. (PubMed, Breast Cancer Res Treat)
Testing cancer susceptibility genes using an agnostic strategy confers a diagnostic benefit for hereditary cancer syndromes compared to phenotype-driven test, without adding complexity to the study. The analysis of healthy individuals with a family history of HBOC detects pathogenic variants in a cost-efficient percentage of cases, resulting in a good alternative strategy when the index case is unavailable.
Journal • BRCA Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
1m
A large-scale genome-wide association study on female genital tract polyps highlights role of DNA repair, cell proliferation, and cell growth. (PubMed, Hum Reprod)
The study findings have the potential to significantly enhance our understanding of the genetic mechanisms involved, paving the way for future functional follow-up, which in turn could improve the diagnosis, risk assessment, and targeted treatment options, since surgery is the only line of treatment available for diagnosed polyps.
Journal
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CHEK2 (Checkpoint kinase 2)
1m
STM2457 impairs the proliferation of esophageal squamous cell carcinoma by activating DNA damage response through ATM-Chk2 axis. (PubMed, Med Oncol)
In tumor-bearing nude mice model, STM2457 combined with Paclitaxel can inhibit the growth of ESCC and increased the expression of ATM and γ-H2AX protein. These findings revealed ATM-Chk2 pathway is a promising therapeutic target for STM2457 to effectively inhibit the proliferation of ESCC.
Journal
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CHEK2 (Checkpoint kinase 2) • METTL3 (Methyltransferase Like 3)
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paclitaxel
1m
Late Recurrent Spitz Melanoma With a TMEM106B::BRAF Fusion. (PubMed, Am J Dermatopathol)
The BRAF fusion supports the diagnosis of Spitz melanoma, a genetically defined subset of Spitzoid melanoma. This case represents the first report of a TMEM106B::BRAF fusion in melanoma, emphasizing the critical role of molecular profiling in diagnosing and managing this malignancy, and suggesting a potential avenue for future therapeutic exploration.
Journal
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BRAF (B-raf proto-oncogene) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)
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BRAF mutation • BRAF fusion
1m
Genome sequencing enhances the diagnostic yield and expands the genetic landscape of male breast cancer. (PubMed, Genet Med Open)
Exome sequencing analysis further identified significant somatic oncogenic drivers and revealed a dominant mutational signature SBS3 across BRCA1/2-negative samples, reinforcing the contribution of omologous recombination deficiency underlying the MBC development. Our findings extended the MBC genetic spectrum beyond BRCA1/2 and highlighted the intricate interplay of monogenic and polygenic predispositions, presenting a comprehensive MBC genomic profile.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • BARD1 (BRCA1 Associated RING Domain 1)
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BARD1 mutation
1m
Exome-based cancer predisposition gene testing can provide a genetic diagnosis for individuals with heterogeneous tumor phenotypes. (PubMed, Eur J Hum Genet)
In conclusion, our study indicates that exome-based cancer predisposition gene testing may aid in the identification of pathogenic variants in individuals who developed multiple primary tumors. Our findings demonstrate that individuals with gPVs in genes associated with cancer predisposition may present with a broad tumor spectrum.
Journal
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PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • FANCM (FA Complementation Group M) • POT1 (Protection of telomeres 1) • RECQL5 (RecQ Like Helicase 5) • RECQL4( RecQ Like Helicase 4) • HOXB13 (Homeobox B13)
2ms
Cholangiocytes' Primary Cilia Regulate DNA Damage Response and Repair. (PubMed, bioRxiv)
Deciliation was induced using shRNA knockdown or CRISPR knockout of IFT20, IFT88, or KIF3A, followed by exposure to the genotoxic agents cisplatin, methyl methanesulfonate (MMS), or irradiation...Deciliated cells exhibit heightened DNA damage, evidenced by increased γH2AX signals and comet assay results, a phenotype mirrored in in vivo IFT88 knockout mice. Furthermore, key DDR regulators, including ATM, p53, and p21, are downregulated in deciliated cells following irradiation, highlighting a crucial role for primary cilia in maintaining genome stability.
Journal • PARP Biomarker
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CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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cisplatin
2ms
Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases. (PubMed, Nat Commun)
At the single-variant level, our study reveals that a rare missense variant in TERT is associated with substantially reduced prostate cancer risk (OR = 0.13 [0.07-0.25], P = 4.67×10-10), and confirms rare non-synonymous variants in a further three genes associated with reduced risk (ANO7, SPDL1, AR) and in three with increased risk (HOXB13, CHEK2, BIK). Altogether, this work provides deeper insights into the genetic architecture and biological basis of prostate cancer risk and severity, with potential implications for clinical risk prediction and therapeutic strategies.
Clinical • Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • HOXB13 (Homeobox B13)
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