A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substit...

Most sporadic breast and ovarian cancers express low levels of the breast cancer susceptibility gene, BRCA1. The BRCA1 gene produces two transcripts, mRNAa and mRNAb. mRNAb, present in breast cancer but not in normal mammary epithelial cells, contains three upstream open reading frames (uORFs) in its 5'UTR and is translationally repressed. Comparable tandem uORFs are characteristically seen in ...

In a screen for gene copy number alterations in mouse mammary tumors initiated by loss of the Brca1 and Trp53 genes, we observed that the majority (11 of 15; 73%) had high-level amplification of wild-type Met, encoding a growth factor receptor implicated in tumor progression. Met amplification was localized to unstable double minute chromosomes and was uniquely found in mouse breast tumors driv...

The genetic etiology of hereditary breast cancer has not been fully elucidated. Although germline mutations of high-penetrance genes such as BRCA1/2 are implicated in development of hereditary breast cancers, at least half of all breast cancer families are not linked to these genes. To identify a comprehensive spectrum of genetic factors for hereditary breast cancer in a Chinese population, we ...

Since its identification in 1994, BRCA1 (Breast Cancer 1) has been established as a familial early onset breast and ovarian cancer susceptibility gene [1]. The protein encoded by this gene is involved in diverse cellular processes such as DNA damage repair, cell cycle control, ubiquitination and transcriptional regulation of target genes [2]. Recently, we uncovered a new function of BRCA1, addi...

There are differences between the histopathology of breast cancers in carriers of BRCA1 and BRCA2 mutations. The findings can be interpreted as breast cancer due to BRCA1 has a different natural history from BRCA2 or apparently sporadic disease, which may have implications for screening and management. Mutations in the BRCA1 gene were implicated as causes of different types of cancers including...

Germline variants within BRCA1 or BRCA2 genes account for approximately 25% of familial aggregations of breast-ovarian cancers. Low or no expression of BRCA1 in breast and ovarian cancers is associated with a good clinical response to treatment with platinum therapies and PARP1 inhibitors. Recent studies demonstrated that microRNAs - small non-coding RNAs, involved in the control of gene expres...

In modern molecular genetics, epistasis analysis is a tool for probing the relationship between two genes and, hence, between the two genes’ products. In its broadest sense, an epistatic relationship exists when combinations of specific alleles of two or more genes generate a quantitative phenotype that differs from the simple addition of phenotypes associated with each individual allele. Many ...

BRCA1 plays a key role in the regulation of p53-dependent target gene transcription activation. Meanwhile, the p53 inducible gene 3 (PIG3) is a downstream target of p53 and is involved in p53-initiated apoptosis. However, little is known about whether BRCA1 can regulate PIG3-mediated apoptosis. Using a tissue microarray containing 149 breast cancer patient samples, we found that BRCA1 and PIG3 ...

PURPOSE A genome-wide scan of 175 hereditary prostate cancer families from the University of Michigan Prostate Cancer Genetics Project provided evidence of prostate cancer linkage to 17q markers near the BRCA1 gene. To examine the possibility that germ-line BRCA1 mutations were associated with hereditary prostate cancer, individuals from 93 families with evidence of linkage to chromosome 17q we...