The tumor suppressor gene tp53 is mutated, deleted, or rearranged in more than 50% of human tumors (1). Wild-type (wt) tp53 stops growth and/or induces apoptosis in most transformed cells into which it is introduced, thus restricting research of such cells. One means of studying the effects of both wt and ...
The fact that human tumor xenografts grown in immunodeficient mice have proven to be useful models of human cancer is well documented. However, the establishment of such xenografts from cell lines cultured in vitro has proven to be fraught with difficulties-these problems become even more a ...
Cytogenetics in ovarian cancer has been restricted to conventional cytogenetic analysis of G-banded metaphase chromosomes up to the early 1980s. The detection of cytogenetic changes in solid tumors was relatively limited, as cytogenetic preparations from solid tumor tissue oft ...
Resulting from problems of low yield of metaphases and poor-quality chromosomes, detection of cytogenetic changes in solid tumors has been relatively limited (1). The advent of fluorescence in situ hybridization (FISH) rendered it possible to obtain “cytogenetic information” from ...
Primed in situ labeling (PRINS) was introduced by Koch and colleagues (1) for the visualization of chromosome centromeres. The concept is based on the knowledge that the alpha satellite repeat monomers at the human centromeres exhibit variation among chromosomes (2), and by targeting such ...
Interphase cytogenetics using formalin-fixed/paraffin-embedded tissue is now a well-established technique, which renders it possible to obtain “cytogenetic information” from interphase nuclei of solid tumors (1,2, for ovarian cancer, e.g., 3-8). It is the only tool to investigate ...
Chromosome microdissection is a recently developed molecular cytogenetic technique that has become increasingly important as a bridge connecting cytogenetics to molecular genetics. After a decade of effort, this approach has been developed into a useful and reproducible appr ...
In 1981, a novel transforming gene called neu, related to, but distinct from, the c-erbB protooncogene, was identified (1-3). In 1985, two groups independently isolated identical erbB-related genes from human DNA that they called HER-2 (4) and c-erbB-2 (5) located at chromosome band 17q11.2 and en ...
The term interphase cytogenetics was first used in 1986 by Cremer (1,2) to describe detection of chromosomal alterations using in situ techniques in interphase nuclei. This was a distinct advantage over conventional analyses as solid tumors could now be studied (2,3) and the possibility of a ...
This chapter is an overview, from a technical perspective, of the approaches that can be used to analyze genetic changes in ovarian cancers. Traditional gene localization methods are discussed, followed by a section on gene identification techniques. Once a putative disease-associat ...
Comparative genomic hybridization (CGH) is a powerful technique for the quantitative detection of changes in chromosome copy number (1-3). It offers an advantage over conventional cytogenetic techniques in the analysis of tumor karyotypes through its utilization of DNA as the mater ...
Many modern analytical methods require little material, which has made feasible biochemical and molecular analyses of small tissue fragments, even individual cells, by microdissection of histological sections (1,2). Polymerase chain reaction (PCR) can potentially be applied ...
Several cell biological studies have shown that the invasiveness of a variety of tumors depend on the regulated expression of proteolytic enzymes that degrade the surrounding extracellular matrix and dissociate cell-cell and/or cell-matrix attachments. One such enzyme, the seri ...
The “two-hit” theory of tumor suppressor gene (TSG) inactivation predicts that loss of function is a result of two separate genetic events, one affecting each allele (1). One hit is commonly a deletion of part of, or the entire allele sequence and can be detected by loss of heterozygosity (LOH) analysis in ...
Study of loss of heterozygosity (LOH) is widely used to identify chromosomal locations of putative tumor suppressor genes. In this type of analysis, DNA extracted from tumor tissue is compared with constitutive DNA from the same patient by the use of polymorphic DNA markers (1). This approach has ...
The p53 tumor suppressor gene encodes a 53-kD nuclear phosphoprotein and is the most commonly altered gene in human cancers (1). There are a large variety of methods currently employed for detection of alterations in thep53 gene. The reported abnormalities in p53 have been detected with a variety ...
Mutations of the p53 tumor suppressor gene are the most common alterations associated with malignancy identified so far. Inactivation of the p53 gene contributes to loss of a cell-cycle check point at the G1-S boundary and to genetic instability of the cell eventually allowing cells to replic ...
Earlier studies with somatic cell hybrids had clearly shown that when malignant cells were fused with normal cells, the resulting hybrid cells were nontumorigenic and that reexpression of tumorigenicity was often associated with the loss of specific chromosomes derived from the nor ...
An association of a loss of DNA replication control and the activation of erbB oncogenes can be deduced from studies with different cancers (1-5). In the first study on ovarian cancer 26% of the tumors had c-erbB-2 amplifications (6). The correlation between c-erbB-2 amplification and expression ...
Although cancer is fundamentally a genetic disease, in the majority of cancers the mutations occur somatically (i.e., only in the tissue from which the cancer is derived). However, for many types of cancer, for example, breast, ovarian, and colorectal cancer there are a small number of cases that ari ...

