Alleles in PTEN and other breast cancer susceptibility genes would be responsible for approximately 25% of the familial component of breast cancer risk, BRCA1 and BRCA2 being the two major genes responsible for this inherited risk.
Also, based on their predictive value of response to therapy, evaluating MGMT and PTEN and learning to interpret their patterns of immunoexpression will undoubtedly lead to a greater understanding of breast cancer and its treatment.
Also, primary breast cancer specimens, all ER positive and HER2 negative, were immunohistochemically investigated for phospho-S6 (pS6) and PTEN, to evaluate the mTOR and PIK3CA/Akt pathways.
Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)--a PTEN-interacting protein and negative regulator of PTEN in breast cancer--as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas.
Analysis on clinico-pathological parameters showed neither HER2 Ile655Val nor PTEN IVS4 genotypes were not associated with any of the variables (p > 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population.
Apparent correlations were detected between AKT and axillary LNM with a tumor size of 2 cm or less; between PTEN, PI3K, and AKT and axillary LNM in stage T1 or T2 breast cancer and invasive carcinoma of a nonspecial type; and between PTEN and AKT and axillary LNM of histologic grade I or II tumors and non-triple-negative breast cancer (all P<.05).
Application of DGCA to the TCGA RNA-seq data in breast cancer not only identifies key changes in the regulatory relationships between TP53 and PTEN and their target genes in the presence of inactivating mutations, but also reveals an immune-related differential correlation module that is specific to triple negative breast cancer (TNBC).
As p53, BRCA1, and PTEN proteins have a key role in preventing breast cancer formation, cancer-associated splicing variants of these tumor suppressor genes are potential molecular markers and may contribute to the development of diagnostic and prognostic methods.
Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status.
BRCA1 and BRCA2 are the genes most commonly associated with inherited breast cancer; however, mutations in TP53 and PTEN cause Li-Fraumeni syndrome and Cowden syndrome, respectively, both of which are associated with high lifetime risks of breast cancer.
BRCA1 and BRCA2 mutations confer very high risks of breast and ovarian cancer. p53 and PTEN mutations lead to very high breast cancer risks associated with rare cancer syndromes.
Breast cancer patients with an identified germline PTEN mutation are at increased risk of endometrial, thyroid, renal, and colorectal cancers as well as a second breast cancer.
By contrast, silencing SALL2 induced downregulation of ERα and PTEN and activated the Akt/mTOR signaling, resulting in estrogen-independent growth and tamoxifen resistance in ERα-positive breast cancer.
Cellular levels of p-AKT(Ser473/Thr308) and p-ERK1/2(Thr202/Tyr204), activating mutations of PIK3CA and inactivating mutations of PTEN may predict response to everolimus in breast cancer cells; these findings have potential applications for treatment personalization of everolimus in breast cancer patients.
Combined, these data indicate that diagnostic or therapeutic chest radiation may predispose patients with decreased stromal PTEN expression to secondary breast cancer, and that prophylactic EGFR inhibition may reduce this risk.
Consequently, new genes have emerged as breast cancer susceptibility genes, including rare germline mutations in high penetrant genes, such as TP53 and PTEN, and more frequent mutations in moderate penetrant genes, such as CHEK2, ATM and PALB2.
Consequently, these results demonstrate that inhibition of Rad51 can sensitize BT549 cells with wild type PTEN to olaparib, which would contribute to using PARP inhibitors in individual treatment of breast cancer patients with PTEN variations.
Consistent with the oncogenic effects in vitro, clinical evidence has confirmed that MCT-1 gene stimulation is correlated with p190B gene promotion and PTEN gene suppression in human breast cancer.
Correspondingly, PTEN knockdown increased stem cell markers, whereas AKT inhibitors compromised the self-renewal ability of CSCs and breast cancer cell lines overexpressing miR-10b.