Amplification of the BCAS2 gene at chromosome 1p13.3-21 in human primary breast cancer.
ABSTRACT BCAS2 is a novel gene isolated from breast cancer cell line by differential display technique. Previously we reported that BCAS2 gene is localized on chromosome 1p13.3-21 and is up-regulated by gene amplification in breast cancer cell lines MCF-7 and BT-20. In this study, we investigated the amplification of the BCAS2 gene in a series of 104 gynecological primary tumors by means of Southern blot analysis. The BCAS2 gene was amplified in two of 60 primary breast cancer tissues, whereas no amplification was detected in any of endometrial (0/26) and cervical (0/18) tumor tissues. Gene amplification was also not detected in a series of pancreatic (0/9) and gastric (0/6) cancer cell lines. An enhanced green fluorescent protein assay revealed that BCAS2 protein seems to be translocated into the nucleus. Although frequent deletions of the proximal region of chromosome 1p13.3-21 have been found in primary breast cancer, our results support first evidence of amplification within this region and indicate that BCAS2 gene codes for a nuclear protein.
- Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 06/1992; 276(3):317-28. · 3.90 Impact Factor
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ABSTRACT: By use of recombinant DNA probes that correspond to genetic loci residing on human chromosome 1, DNA samples from 37 ductal breast carcinomas and constitutional DNA from the same individuals were tested for loss of heterozygosity. A high frequency (41%) of reduction to homozygosity was detected with the probe p1-79, which recognizes the highly polymorphic locus D1Z2, localized on 1p36. Loss of heterozygosity at other chromosome 1 loci was much less common, not exceeding a frequency of 10%, and was never observed in the absence of the D1Z2 loss. Somatic loss of heterozygosity at D1Z2 was more frequent in patients with a strong family history of breast cancer (60%), in patients with early diagnosis (before 45 years of age) (70%), and in those with multiple tumors or tumor foci (50%) than in patients with none of the characteristics of hereditary tumors (21%). No associations were observed between loss of heterozygosity and prognostic factors. These results suggest that inactivation of a tumor suppressor gene located on the distal portion of chromosome 1p, alone or combined with other genetic changes, may represent a fundamental step in the pathogenesis of ductal carcinoma of the breast.The American Journal of Human Genetics 08/1989; 45(1):73-82. · 11.20 Impact Factor
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ABSTRACT: The conditional expression of activated HER2/neu gene under its endogenous promoter in the mammary epithelium of the mouse results in accelerated lobular development and focal mammary tumors. Carcinogenesis, however, requires amplification and considerably increased expression levels of oncogenic neu. Deducing from the multiple genetic aberrations required for human breast cancer to develop, we hypothesized that in addition to the over-expression of an activated HER2/neu, secondary aberrations would occur. We have therefore conducted a genomic screen for chromosomal imbalances and translocations using comparative genomic hybridization and spectral karyotyping. The results reveal a moderate degree of chromosomal instability and micronuclei formation in short-term cultures established from primary tumors. Genomic instability appears to be linked to the amplification of functional centrosomes, a phenomenon that we frequently observed in other tumor types. Seventy per cent of the tumors revealed genomic amplification of HER2/neu, often in the form of double minute chromosomes, which correlated with recurring loss of mouse chromosome 4D-E, a region that is orthologous to distal human chromosome 1p. It is likely that this region contains putative tumor suppressor genes whose inactivation is required for tumor formation in this model of human breast cancer.Oncogene 02/2002; 21(6):890-8. · 7.36 Impact Factor