Promoter Methylation Status in 1031 Primary Breast Cancers Predicts Favorable Outcomes Following Chemotherapy.

Background: Breast Cancer 1 gene () is known to be inactivated in breast tumors by promoter methylation. Tumor cells in patients carrying a germline mutation in are sensitive to cytotoxic drugs that cause DNA double strand breaks. However, very little is known on whether patients with promoter methylated tumors are similarly sensitive to cytotoxic drugs.

CpG promoter methylation of the ALKBH3 alkylation repair gene in breast cancer.

Background: DNA repair of alkylation damage is defective in various cancers. This occurs through somatically acquired inactivation of the MGMT gene in various cancer types, including breast cancers. In addition to MGMT, the two E.

A DNA methylation-based definition of biologically distinct breast cancer subtypes.

In cancer, epigenetic states are deregulated and thought to be of significance in cancer development and progression. We explored DNA methylation-based signatures in association with breast cancer subtypes to assess their impact on clinical presentation and patient prognosis. DNA methylation was analyzed using Infinium 450K arrays in 40 tumors and 17 normal breast samples, together with DNA copy number changes and subtype-specific markers by tissue microarrays.

CpG island hypermethylation of BRCA1 and loss of pRb as co-occurring events in basal/triple-negative breast cancer.

Triple-negative breast cancer (TNBC) occurs in approximately 15% of all breast cancer patients, and the incidence of TNBC is greatly increased in BRCA1 mutation carriers. This study aimed to assess the impact of BRCA1 promoter methylation with respect to breast cancer subtypes in sporadic disease. Tissue microarrays (TMAs) were constructed representing tumors from 303 patients previously screened for BRCA1 germline mutations, of which a subset of 111 sporadic tumors had previously been analyzed with respect to BRCA1 methylation.

Breast cancer risk associated with AURKA 91T -->A polymorphism in relation to BRCA mutations.

In this study 759 breast cancer patients, including 9 BRCA1 and 98 BRCA2 mutation carriers, and 653 mutation-negative unaffected controls were genotyped for the AURKA 91T -->A polymorphism. Individuals homozygous for the 91A allele were found to be at increased risk of breast cancer compared to 91T homozygotes (OR=1.87; 95% CI=1.

Aurora-A amplification associated with BRCA2 mutation in breast tumours.

Potential interaction of Aurora-A amplification and BRCA2 mutation was examined in breast tumours from BRCA2 999del5 mutation carriers (n=20) and non-carriers (n=41). Aurora-A amplification studied by FISH was significantly more common in breast tumours from BRCA2 mutation carriers (p=0.0005).

Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer.

Introduction: BRCA1 or BRCA2 germline mutations increase the risk of developing breast cancer. Tumour cells from germline mutation carriers have frequently lost the wild-type allele. This is predicted to result in genomic instability where cell survival depends upon dysfunctional checkpoint mechanisms.

Effect of hypoxia and TP53 mutation status and cytogenetics of normal and malignant mammary epithelium.

It has been proposed that hypoxia favors the growth of tumor cells over normal cells, particularly tumor cells carrying TP53 mutations. Cytogenetic studies of breast cancer have shown that highly complex karyotypes seen in direct harvest preparations are rarely detected after short-term culture. In this study, 34 paired samples of breast carcinomas and grossly nontumorous tissue from the same breast were cultured at 20 and 5% (12 samples) or 20 and 0% oxygen (22 samples).