Alternative titles; symbols
HGNC Approved Gene Symbol: VWA5A
Cytogenetic location: 11q24.2 Genomic coordinates (GRCh38): 11:124,115,450-124,147,721 (from NCBI)
Chromosomal deletions in chromosomal segment 11q23 are associated with various human tumors. In lung and breast carcinomas, 2 common regions of loss of heterozygosity have been identified at 11q23, suggesting that the same tumor susceptibility genes are altered in these malignancies. Monaco et al. (1997) stated that the more distal of these 2 regions, region 2, spans less than 1.7 Mb. They identified a cDNA from region 2 and designated it LOH11CR2A. The cDNA encodes a predicted 438-amino acid protein. Northern blot analysis revealed that LOH11CR2A is expressed ubiquitously as a 3.3-kb mRNA.
Martin et al. (2003) found that, unlike the human BCSC1 gene, mouse Bcsc1 is expressed as a single mRNA transcript of approximately 4 kb and encodes a 793-amino acid protein with a predicted molecular mass of 87 kD.
Monaco et al. (1997) reported that the LOH11CR2A coding region is composed of 10 exons and spans 30 to 40 kb. There are at least 2 additional exons encoding the 5-prime untranslated region.
Contrary to the original characterization of the LOH11CR2A gene (Monaco et al., 1997), Martin et al. (2003) found that the gene, which they called BCSC1, contains 20 exons instead of 10 and possesses a larger open reading frame. The mouse gene was found to span a genomic region of 25 kb and to comprise 20 exons also.
Monaco et al. (1997) identified the LOH11CR2A gene within a region of chromosome 11q23 associated with various human tumors.
Based on a mutation analysis of multiple human carcinomas and tumors, Monaco et al. (1997) concluded that LOH11CR2A is unlikely to be involved in the tumorigenic process.
By constructing a physical map of the LOH11CR2 minimal region of loss on 11q23-q24 associated with lung and breast carcinomas, Martin et al. (2003) were able to clone a hereditary translocation, t(11;12)(q23;q24), from a patient with early-onset breast cancer and family history of cancer. The breakpoint was found within 6 kb of the BCSC1 candidate tumor suppressor gene located in the LOH11CR2 region, whereas additional LOH analysis in breast and ovarian tumors, including that of the patient with the t(11;12)(q23;q24) translocation, implicated the BCSC1 locus as the primary target of deletion. Northern analysis of the BCSC1 mRNA revealed a lack of expression in 33 of 41 (80%) tumor cell lines, and its ectopic expression led to the suppression of colony formation in vitro and tumorigenicity in vivo. These data suggested that BCSC1 may exert a tumor suppressor activity and is a likely target of the LOH observed on 11q23-q24 in cancer. Martin et al. (2003) used tumor biopsies available from breast and ovarian cancer patients used in the LOH analysis to screen for mutations in the BCSC1 coding region by PCR and direct sequencing. Several previously reported polymorphisms were found, although no tumor-specific, somatic mutations were observed. Other results indicated that the mechanism for BCSC1 gene inactivation in tumor cells is the loss of gene expression of one allele and deletion of the other.
Martin, E. S., Cesari, R., Pentimalli, F., Yoder, K., Fishel, R., Himelstein, A. L., Martin, S. E., Godwin, A. K., Negrini, M., Croce, C. M. The BCSC-1 locus at chromosome 11q23-q24 is a candidate tumor suppressor gene. Proc. Nat. Acad. Sci. 100: 11517-11522, 2003. [PubMed: 14504409] [Full Text: https://doi.org/10.1073/pnas.1934602100]
Monaco, C., Negrini, M., Sozzi, G., Veronese, M. L., Vorechovsky, I., Godwin, A. K., Croce, C. M. Molecular cloning and characterization of LOH11CR2A, a new gene within a refined minimal region of LOH at 11q23. Genomics 46: 217-222, 1997. [PubMed: 9417908] [Full Text: https://doi.org/10.1006/geno.1997.5036]