Detection of somatic DNA alterations in ovarian cancer by DNA fingerprint analysis

Article Abstract:

Many cancers, if not all, are thought to arise from the mutation of cellular genes. Indeed, it is generally thought that not one, but a series of mutations is necessary to result in a cell leaving the straight and narrow path and traveling towards malignancy. There are reasons to expect that some of the initial events in the development of cancer may involve an increase in the instability of a cell's genetic makeup, which would render further mutations that much more likely. Often the effects of these mutations can be discerned by karyotyping, which is the analysis of the appearance of chromosomes under the microscope. However, while it is easy to prepare chromosomes for study from tumors such as leukemia, it is technically difficult to do the same for solid tumors, and thus less is known about the karyotypes, or chromosome content, of the cells of solid tumors. Fortunately, molecular biology has provided techniques that do not depend upon the preparation of chromosomes as a means of demonstrating genetic changes. One such technique is the preparation of DNA fingerprints, in which highly specific enzymes are used to cleave the DNA into specific pieces of characteristic size. Just like human fingerprints, no two different sources of DNA are likely to yield the same set of fingerprint fragments. Rather than consider the myriad of fragments that comprise the human genome, the authors examined only those fragments that were recognized by a specific marker, in this study the so-called minisatellite sequences. They used the technique to look for signs of genetic changes in 20 patients with ovarian cancer. When the DNA from the ovarian cancer specimens was processed, an average of 22 fragments containing these minisatellite sequences could be identified. When the DNA fragments from the tumors were compared with the fragments from the patients' normal cells, changes were detected in 12 of the 20 specimens. In seven cases, one or more fragments was missing from the tumor DNA, in two cases new DNA fragments appeared, and in eight cases a shift in intensity was observed. The authors suggest that the application of DNA fingerprint analysis may be a useful starting place for the examination of genetic changes in solid tumors. (Consumer Summary produced by Reliance Medical Information, Inc.)

Usage, Physiological aspects, Ovarian cancer, DNA testing, DNA identification, DNA damage

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Seeking tumor genes with DNA technology

Article Abstract:

Raymond L. White was a recipient of the Charles S. Mott Prize, awarded by the General Motors Cancer Research Foundation to recognize contributions in cancer research. In his prize-winner's lecture, White described the contribution which DNA technology has made to the study of the genetic basis of some cancers. Traditionally, the identification of genes which were responsible for heritable cancers required the use of a myriad of markers for genetic traits for which the chromosomal location was known. By studying sufficiently many family members, it might be possible to demonstrate that the cancer gene was likely to be linked to (that is, usually inherited with) some other known gene. DNA technology has vastly improved upon this technique. Instead of using markers of known genetic traits, it is now possible to achieve the same task more efficiently and also more precisely using restriction fragments. These fragments of DNA, prepared by the digestion of DNA with special enzymes, can be used to follow the inheritance of specific regions of DNA from one generation to the next. Without having to rely upon known genetic traits, it is now possible to find the "linkage" of the cancer gene quickly with greater precision than has been previously possible. Using this method, researchers have located and studied the genes for a variety of familial human cancers. One such cancer is type 1 neurofibromatosis. This gene has turned out to be an especially large gene located on chromosome 17. The size of this gene is consistent with the high frequency of mutations of the neurofibromatosis gene which occur in the general population. The same method has been used to locate the gene for familial adenomatous polyposis, a genetic condition in which patients have many intestinal polyps which have a high risk of transforming into colon cancer. This gene has been located to chromosome 5, and it is now possible to check this gene locus when new families with familial colon cancer are identified. The use of restriction fragments of DNA to map out the genes on the chromosomes will play a central role in mapping the entire collection of human genes in the Human Genome Project. (Consumer Summary produced by Reliance Medical Information, Inc.)

Methods, Cancer, Cancer genetics, Chromosome mapping, Genetic disorders, Proto-oncogenes, Oncogenes, Medical genetics

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