Disease relevance of BRCA1

• Five to ten percent of breast cancer in the western world may be attributed to the inheritance of highly penetrant mutations in the breast and ovarian cancer susceptibility gene, BRCA1 [1].
• The breast and ovarian cancer susceptibility gene product BRCA1 is a tumor suppressor, but its precise biochemical function remains unknown [2].

High impact information on BRCA1

• The distribution of missense mutations and neutral polymorphisms identified in BRCA1-linked breast cancer suggests that disease associated missense mutations occur at highly conserved residues whereas polymorphisms are in regions of lower conservation [1].
• These results raise the possibility that loss of transcription activation by BRCA1 is crucial for oncogenesis [2].
• Therefore, identification of residues involved in transcription activation by BRCA1 will help understand why particular germ-line missense mutations are deleterious and may provide more reliable presymptomatic risk assessment [2].
• Functional assay for BRCA1: mutagenesis of the COOH-terminal region reveals critical residues for transcription activation [2].
• Since the identification of the human breast and ovarian cancer gene, BRCA1, a large spectrum of germline mutations has been characterized that predispose women to developing these diseases [3].

Biological context of BRCA1

• We have also identified several putative regulatory elements through comparison of the bidirectional BRCA1 promoter regions among the rat, mouse, and human genes [3].
• BRCA1 is a nuclear phosphoprotein that participates in the regulation of the cell cycle [4].
• Microsatellite polymorphism in intron 14 of the canine BRCA1 gene [5].
• Microsatellite polymorphism due to differences in CT dinucleotide repeats was demonstrated in intron 14 of the canine BRCA1 gene [5].
• 1. This polymorphism, which occurs at the intron of canine BRCA1 should prove to be a useful marker for detecting the loss of heterozygosity (LOH) [5].

Anatomical context of BRCA1

• The present study examined immunohistochemically the expression and intracellular distribution of BRCA1 protein in two normal, seven dysplastic and 44 neoplastic canine mammary glands and its relationship with clinical and pathological variables and other prognostic parameters [4].
• Strong nuclear immunolabelling of BRCA1 protein was observed in the epithelial cells of the normal mammary glands and mammary dysplasias [4].

Analytical, diagnostic and therapeutic context of BRCA1

• The biological function of BRCA1 and factors affecting expressivity, such as gene-environment and gene-gene interactions, may be more effectively studied in appropriate animal models [1].

References