In the past year significant progress has been made molecular cytogenetics and molecular biology of cancer cells. The distribution of 13 POTE (expressed in prostate, ovary, testis and placenta) paralogous genes was determined in prostate carcinoma cell lines, to see whether gene activation is dependent on gene rearrangements. Lack of POTE rearrangements in a cell line with many chromosomal abnormalities indicated a different mechanism was responsible for POTE activation. The transfer an 85-kb bacterial artificial chromosome clone, containing a cell senescence gene (SEN16) on chromosome 16q24, into breast cancer cells resulted in growth arrest and the cellular alterations characteristic of cell senescence. The human AKNA gene that encodes a lymphoid-specific AT-hook transcription factor was mapped to human chromosome 9q32 at fragile site FRA9E. Damage and gene recombination at fragile sites are associated with the development of neoplasia. Recurrent chromosome changes involving several genes that are implicated in human thyroid cancer were identified in a mouse model for thyroid cancer thus providing new insights in human thyroid cancer. A recurrent translocation t (5; 19) was also identified in a carcinoma cell line derived from a spontaneous mouse mammary tumor. This translocation is instrumental to the activation of Fgf8 gene and acquisition of androgen dependency in mammary cells. DLC-1 (deleted in liver cancer) was cloned in our laboratory and shown to function as a tumor suppressor gene in liver, breast, lung, ovarian, nasopharyngeal, esophageal, and cervical cancer. Our new data demonstrated that DLC-1 also functions as a metastasis suppressor gene in breast cancer and is down regulated and silenced in large number prostate cancer patients due to promoter hypermethylation and histone deacetylation. These results suggest that DLC-1 may have clinical applications in prevention of breast cancer metastasis, the major cause of cancer death, and its aberrant methylation may provide a useful biomarker for early detection of prostate cancer. Targeted disruption of the DLC-1 gene in mice resulted in to embryonic lethality at mid-gestation, showing that this Rho GAP gene is essential for embryonic development in mammals. Two additional members of the DLC family have recently been identified, DLC-2 and DLC-3, that are approximately 50% identical to DLC-1. Using a cancer-profiling array, we detected down regulation of DLC-1 expression in lung, renal, uterine, ovarian, and breast cancers and down-regulation of DLC-2 expression in lung, ovarian, renal, uterine, gastric, colon and rectal tumors. In addition, decreased expression of both genes was found in prostate tumors, thus underlining the wide involvement of this family of genes in various human cancers. We had previously found that the mouse Gtf2ird1 gene was disrupted in a line of c-myc transgenic mice. Gtf2ird1 is the mouse homolog of one of the genes hemizygously deleted in the developmental disorder Williams-Beuren syndrome (WBS). Detailed analysis of the Gtf2ird1-null transgenic mice showed that they exhibited abnormalities of the skull and jaws similar to those of WBS patients, indicating that Gtf2ird1 may have a role in craniofacial development in humans and mice. New insights into hepatitis C virus (HCV) infection in B-lymphocytes were obtained. In a collaborative study it has been demonstrated that HCV core significantly inhibited B-lymphocyte apoptosis and dramatically down-regulated MHC class II molecules in B cells expressing HCV core while the expression of immunoglobulin genes was not significantly altered. Meanwhile, genes associated with leukemia and B-lymphoma were consistently up regulated by HCV core.
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