KEY POINTS: Germline mutations detected in pediatric gliomas may represent a cancer predisposition syndrome.Integrating molecular testing into routine clinical care for pediatric patients with glioma is critical to identify therapeutic targets and patients with a cancer predisposition syndrome.Patients with glioma with defects in DNA repair pathway components (e.g., <i>BRCA1/2</i>) may show increased responsiveness to poly (ADP-ribose) polymerase (PARP) inhibitors.Combining PARP inhibitors with temozolomide (standard-of-care treatment) revealed no adverse events or toxicities over the course of 18 months.
We irradiated HT1080, M059K (DNA-PKcs<sup>+/+</sup>), and HCC1937 human cancer cell lines and their isogenic counterparts HT1080-shDNA-PKcs, HT1080-shRAD51<sup>IND</sup>, M059J (DNA-PKcs<sup>-/-</sup>), and HCC1937-BRCA1 (BRCA1 complemented) to assess cell clonogenic survival and γ-H2AX radiation-induced foci.
This method is useful for identifying BRCA1 deficiencies and localization in a variety of research fields, including development, neurodegeneration, and cancer.
Factors that predicted for BRCA1/2 mutations were: breast and ovarian cancers in the same patient (p = 0.031), young age of EOC (p = 0.029), menstrual status (p = 0.004) and family history of cancer (p < 0.0001).
Our findings help to explain the association of this variant with a lower cancer risk in BRCA2 mutation carriers and highlight the importance of genetic changes in BER pathway genes as modifiers of cancer susceptibility for BRCA1 and BRCA2 mutation carriers.
We have found that BRCA1, a multifunctional protein involved in DNA repair and epigenetic regulation, plays a critical role in the regulation of cancer stem cell (CSC)-like characteristics.
Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants.
The neXtProt Cancer variant portal ( https://www.nextprot.org/portals/breast-cancer ) contains over 6300 observations at the molecular and/or cellular level for BRCA1 variants.
Importantly, these nanoparticles could (i) overcome resistance to antiangiogenic therapy, (ii) prevent antiangiogenic therapy-induced increases in cancer stem-like cells in both murine and human tumor cell models, (iii) prevent antiangiogenic therapy-induced increases in VEGF-C, and (iv) prevent antiangiogenic therapy-induced BRCA1 gene expression.
BRCA1/2 genes are the most commonly mutated pancreatic cancer susceptibility genes that should be considered in all pancreatic cancer cases with young age at onset or a family history of cancer.
The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found.
Formalin-fixed paraffin-embedded cancer tissue can undergo testing within a routine molecular-diagnostic setting as a clinical BRCA1/2 mutation screening strategy.
BRCA1/2 mutations seem not to be significantly involved in hereditary breast cancer in the GCC countries, which is the most reported form of cancer in Oman, however no available data about the BRCA1/2 mutations role in breast cancer in the UAE.
In this study we surveyed 193 BRCA1/2 mutation carriers in the state of Tasmania to determine the uptake of cancer risk-reducing strategies and what factors might influence women's decisions in relation to both gynaecological and breast surgery.
<i>BRCA1</i> and <i>BRCA2</i> (<i>BRCA1/2</i>) variants classified ambiguously as variants of uncertain significance (VUS) are a major challenge for clinical genetic testing in breast cancer; their relevance to the cancer risk is unclear and the association with the response to specific <i>BRCA1/2</i>-targeted agents is uncertain.