Although BRCA1 acts as a tumor suppressor and is present in all cells, where it is essential for the maintenance of the genome integrity, it is still not clear why mutations in the BRCA1 gene predispose to breast and ovarian, but not to other types of cancer.
The presence of p16 mutations in esophageal metaplastic columnar epithelium without goblet cells suggest that this pathology may have malignancy potential.
Previous results showed that p19 did not interact with two known p21 effectors, Raf1 and Rin1, but was shown to interact with RACK1, a scaffolding protein that promotes multi-protein complexes in different signaling pathways (Cancer Res 2003, 63 p5178).
The potentially high efficacy and low toxicity of poly(ADP-ribose) polymerase inhibitors presents an opportunity for targeted cancer therapeutics for BRCA1 and BRCA2 germline mutation carriers.
The results of our meta-analysis demonstrated that the frequencies of p15 (INK4b) and p16 (INK4a) promoter methylation in cancer samples were significantly higher than in normal samples (p15 (INK4b) : OR = 6.26, 95 %CI = 3.87 ~ 10.12, P < 0.001; p16 (INK4a) : OR = 2.26, 95 %CI = 1.22 ~ 4.20, P < 0.001).
Epidermal growth factor receptor (EGFR) is usually expressed in squamous cell anal carcinoma (SCAC) and anti-EGFR agents could represent a valid treatment strategy, also considering that KRAS and BRAF mutations are rare events in this type of cancer.
An integral role for miRNAs in cancer pathogenesis is well established; however, the role of miRNAs in KRAS-mediated tumorigenesis is poorly characterized.
Expression of patient-derived GNB1 variants in Cdkn2a-deficient mouse bone marrow followed by transplantation resulted in either myeloid or B cell malignancies.
Women with germline mutations in the cancer susceptibility genes, BRCA1 or BRCA2, associated with Hereditary Breast & Ovarian Cancer syndrome, have up to an 85% lifetime risk of breast cancer and up to a 46% lifetime risk of ovarian, tubal, and peritoneal cancers.
The activation status of signal transduction pathways involving receptor tyrosine kinases and its association with EGFR or KRAS mutations have been widely studied using cancer cell lines, although it is still uncertain in primary tumors.
Taken together, our data suggest disruption of BRCA1 and/or BRCA2 gene expression in certain epithelial cancer cell lines of the ovary, prostate, and breast.
Parallel analyses of other germline variants in the PALB2 N-terminal BRCA1-binding domain identified multiple variants that affect HR function to varying degrees, suggesting their possible contribution to cancer development.
Since its discovery as an inhibitor of cyclin-dependent kinases 4 and 6, the tumor suppressor p16 has continued to gain widespread importance in cancer.
Also, BRCA1-associated tumors more frequently were of larger size (p = 0.041) and higher grade of malignancy (p = 0.005) than non-BRCA1-associated tumors.
In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases.
It has been reported that p16 protein is overexpressed in many types of solid cancer and its aberrant expression may trigger the immune response, leading to the secretion of anti-p16 antibodies.
However, p16 may also be expressed in some benign leiomyoma variants such as leiomyomas with bizarre nuclei and cellular leiomyomas, limiting its utility as a biomarker to distinguish between benign and malignant neoplasms.
Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies.
This repeated-measures study examined cancer genetics knowledge and beliefs before and after counseling and their relationship to receipt of results for BRCA1/2 mutations in 120 highly educated Ashkenazi Jewish individuals.
The results revealed significant differences between normal bladder mucosa (100%) and cancer tissue (40.3%) for the positive staining of p16 protein (p < 0.001), while positive staining for the cyclin D1 protein in the patient group (67.2%) was significantly higher (p = 0.003) than that in the control group (16.7%).