Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

Women who carry mutations in the BRCA1 gene on chromosome 17q have an 85% lifetime risk of breast cancer, and a 60% risk of ovarian cancer. We have identified BRCA1 mutations in 12 of 30 (40%) Canadian families with breast and/or ovarian cancer, including six of the eight families (75%) that contained two cases of early-onset breast cancer and two cases of ovarian cancer. Six frameshift mutations account for all 12 mutant alleles, including nucleotide insertions (two mutations) and deletions (four mutations). Four independent families carried the same 1 basepair (bp) insertion mutation in codon 1755 and four other families shared a 2 bp deletion mutation in codons 22-23. These families were not known to be related, but haplotype analysis suggests that the carriers of each of these mutations have common ancestors.

The decrease in FVIII and RBC 2,3-DPG can be acceptable as a compromise to improve blood component logistics, but leukoreduction efficiency must be improved before considering the adoption of an overnight storage of WB before PRP processing.

This study demonstrates distinct virus-inducible enhanson properties for three regions of the human beta interferon (IFN-,B) promoter; maximum vrus inducibility required syngerism among all three enhansons. Expression of the ERF-1 transcription factor differentially increased the expression of plasmids containing (AAGTGA)4 or PRDM (-94 to -78) motifs but was inefficient in the induction of the intact IFN-0 promoter.The human T-cell (11,14,38,41). The contribution of an individual enhanson to overall enhancer activity may vary in a cellspecific manner, reflecting the relative abundance and/or activity of specific transcription factors. Four distinct classes of enhansons have been described. Class A enhansons display strict spacing requirements and exhibit enhancer activity when tandem repeats of the motif are oligomerized. Class B enhansons exhibit no enhancer activity when multimerized on their own but can generate enhancer activity when juxtaposed with class A motifs (to form a proto-enhancer) and then oligomerized. Class C enhansons possess intrinsic proto-enhancer activity and, when oligomerized, form a functional enhancer element without strict spacing requirements between enhansons. Class D enhansons, exemplified by steroid response elements, display enhancer activity once the receptor is bound (14,31,36,41).Virus-induced activation of beta interferon (IFN-P) transcription is mediated by the interaction of regulatory proteins with enhanson elements in the IFN-1 promoter. In particular, a hexameric sequence, AAGTGA, permutations of which are present throughout the IFN-P promoter between -107 and -65 relative to the mRNA start site, can function as a virus-inducible or constitutive enhancer when present in tandem repeats (12,20). Multimers of the AAGTGA hexamer generate the sequence GAAAGT, which * Corresponding author.is thought to represent a high-affinity site for two DNAbinding proteins, 18,19,26,39). Recently, different types of (GAAANN)4 sequences mediating virus inducibility have been described, indicating that different hexameric sequences are not equivalent and that other IRF-like proteins are involved in alpha interferon and IFN-,B induction (37).The natural IFN-P promoter contains an interferon regulatory element (located at -77 to -37) which includes two positive regulatory domains (PRDI and PRDII) and one negative regulatory domain, as defined by mutational analysis and protein-DNA interactions (21,22,33,48,49). The PRDI domain (-77 to -64) is thought to interact with the IRF proteins (19,26,39,48), as well as with other constitutive and inducible factors (33,37,48). The PRDII domain (5'-GGGAAATTCC-3'; -64 to -55) binds NF-KB, a cellular factor involved in the transcriptional activation of several viral and cellular genes (3,6,30,32,40,43 (16,28,34,46