Retinoblastoma Gene Rb Research Articles

Detailed Molecular Delineation of 13q14.3 Loss in B-Cell Chronic Lymphocytic Leukemia

AbstractA region of chromosome 13q14.3, telomeric to the Retinoblastoma gene RB-1 is frequently deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). A cosmid and P1-derived artificial chromosome (PAC) contig spanning over 600 kb has been constructed, which encompasses this locus. The contig clones have been used to order a number of markers along the minimally deleted region and to localize a series of CpG islands corresponding to possible candidate genes. A novel polymorphic dinucleotide repeat, 6E3.2, present in one of the ordered cosmid clones has been isolated for use in deletion mapping studies of patient DNA. Leukemic samples from 229 CLL patients have been screened for loss of heterozygosity using microsatellite markers and analyzed for hemizygous and homozygous deletions by Southern blot techniques using genomic probes selected from cosmids across the region. Hemizygous deletions were found in 31% of cases with an additional 10% showing homozygous loss. The use of these probes has defined the commonly deleted area to less than 130 kb, centromeric to the locus D13S272.

The role of proto-oncogenes in coronary restenosis

Arterial injury results in exposure of medial smooth muscle cells and adventitial fibroblasts to multiple growth factors that bind to specific cell surface receptors. These in turn activate second messengers and induce expression of immediate-early genes within minutes to hours after ligand binding to the receptor. Activation of the immediate-early genes results in passage of the stimulated cell from its nonproliferating, quiescent G0 state to the first phase of the cell cycle (G1). Coordination of the events that occur during the cell cycle is effected by a series of cyclin-dependent kinases and requires inactivation of several "tumor suppressor genes," including p53, p21, p16, p15, p27, and the retinoblastoma gene Rb, that inhibit the kinase activity of the cyclin/Cdk complexes. An understanding of the factors that regulate signal transduction, cell cycle progression, and programmed cell death has suggested several novel therapeutic strategies including (1) antisense oligonucleotide inhibition of proto-oncogene expression, (2) the use of molecular decoys or pharmacological therapies to block specific steps required for cell cycle progression, and (3) gene transfer of tumor suppressor genes. The apparent success of several of these strategies in animal models of restenosis suggests that these molecular therapies may play a valuable role in preventing intimal hyperplasia and restenosis after balloon angioplasty and vascular stenting.

Osteosarkom bei zwei Geschwistern

With a brother and sister, osteosarcoma developed at the age of 11 and 14 respectively. With both there was no previous retinoblastoma or other bone disease with a proclivity to develop osteosarcoma. We discuss possible explanations for familial aggregation of osteosarcoma, citing external or genetic factors. We suggest that it is the retinoblastoma gene RB and the tumor suppressor gene p53 which play an important part in the development of osteosarcoma.

Molecular biology of breast cancer

A gene responsible for an inherited predisposition to breast and ovarian cancer has been localized to the long arm of chromosome 17 and termed BRCA1. As well as being closely linked to breast/ovarian cancer cases, this gene may be involved in up to 45% of site-specific breast cancers. The identification and cloning of the BRCA1 gene is imminent, and will facilitate the screening and counselling of families at risk of breast cancer, and in the longer term may open up new therapeutic possibilities. The tumour suppressor gene TP53 is mutated in 25%-40% of cases of sporadic breast cancer, and is associated with an aggressive tumour phenotype and poor prognosis in both node-positive and node-negative cases. The pattern of mutations in this tumour suppressor gene shows a higher than expected frequency of G to T transversions, mostly restricted to the highly conserved domain in exons 5 to 8. In many, but not all cases, point mutation of one allele is accompanied by deletion of the remaining normal allele at chromosome 17p13. Abnormalities of TP53 appear to be relatively early events in tumorigenesis, being present in ductal carcinoma in situ lesions. The retinoblastoma gene RB1 shows a variety of abnormalities in about 20% of breast cancers, and there may be an association with TP53 mutations. Other abnormalities which occur with a particularly high incidence in breast cancer include allele loss at chromosome 1p/1q, 3p, 6q, 11p, 16q and 18q. The ERBB2 oncogene encodes a transmembrane receptor tyrosine kinase whose ligand has recently been claimed to be the heregulin family in man.(ABSTRACT TRUNCATED AT 250 WORDS)

A new G to T polymorphism in the retinoblastoma gene RB1 detected by DGGE.

A new G to T polymorphism in the retinoblastoma gene RB1 detected by DGGE.