Introduction.
Introduction.
The Emory University Hospital Oncology Cytogenetics Laboratory provides services of cytogenetics testing of suspected malignant tissue to variety of clients, including patients, physicians, and students.
With commitment to excellence, our services shall be distinguished by our ability to provide rapid test results without loss of quality. Through our skilled technical staff and modern laboratory facility, our department shall be able to achieve its ultimate purpose of providing thorough, state-of-the-art diagnostic services. |
TO CREATE a high quality oncology cytogenetic diagnostic facility for the analysis of chromosome abnormalities in suspected malignant tissue. Paramount attention is given to utilization of laboratory techniques which provide adequate numbers of metaphase cells, maximum ban resolution along with careful attention to quality control and quality assurance measures. In this manner, reliable and rapid cytogenetic testing can be offered, which can aid in the diagnosis and management of patients in whom known there is suspected malignancy. |
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| Introduction
Cancer is the result of mutation involving genes related to regulation of cell growth. Cancers form when these genes are altered permitting cells to grow out of control. A cancer mutation may originate as an acquired abnormality in a somatic cell at any point during an individuals' life span; or a cancer mutation may be present at birth as a germline (constitutional) abnormality. Germline mutations are transmitted in families, thus accounting for inherited cancer. The ultimate impact of cancer mutations (acquired or constitutional) may be modulated by environmental factors as well as genetic events. Most cancer mutations are small, in some instances involving alteration of a single DNA basepair. Such mutations can only be detected by molecular techniques. Other cancer mutations involve a large enough segment of DNA that the defect can be observed by studying the chromosomes in the microscope with cytogenetic approaches. These latter abnormalities are the focus of this discussion. Because many of the caner-related cytogenetic abnormalities are specific for a particular disease, cytogenetic analysis of malignant tissue is a valuable techniques for making accurate diagnoses. In addition, as cytogenetic abnormalities may disappear during remission and reappear during relapse, cytogenetic montoring is a useful tool for accessing disease status. |
| Methods
Cytogenetic analysis of malignant tissue is accomplished by culturing cells form blood, bone marrow or solid tissue for periods of one to several days. Colcemid is added during the final stage of the culture to arrest cells in metaphase, the point in the cell cycle when chromosomes are condensed and can be observed as distinct units. The metaphase cells are exposed to a hypotonic solution, fixed applied to microscope slides and stained with a nuclear dye (frequently Giemsa stain). Microscopic analysis includes evaluation both the number of chromosomes per cell and the morphology of each chromosome. Chromosome morphology is determined by the position of the centromere which creates a short arm (p) and log arm (q) as well as by special staing procedures referred to as banding techniques which permit precise identification of each chromosome and the identification of sub-chromosomal regions. Abnormalities of chromosome structure are recognized by alterations in the pattern of bands, regions of differential staining along the length of the chromosome. Clonal abnormalities of either chromosome number or structure may be indicative of a malignant process. Cytogenetic abnormalities may also be detected by the technique of fluorescence in-situ hybridization (FISH). With this method, a DNA probe specific for a particular chromosome, chromosome region, or gene is hybridized to the DNA of a metaphase spread or a non-dividing interphase cell. The probe will hybridize only to regions where the cell DNA is complementary to the probe. The hybridizartion reaction is detected by a fluorescent reaction. By this method, abnormalities involving genetic regions smaller than chromosomal bands can be observed. Several hundred different recurring cytogenetic abnormalities (involving nearly every chromosome) have been described in cancer. The DNA at or near the breakpoint sites of these abnormalities is the locus of genes related to cell growth, differentiation, or cell death (apoptosis). A great deal has been learned about the development of cancer by studying both the chromosome abnormalities and the molecular consequences of the altered genes produced by the cytogenetic changes. In the following section a few of the most well described cancer-relateed chromosome abnormalities are described. |
| Conclusion
Due to the specificity of many of the cancer-related chromosome abnormalities, cytogenetic evaluation is an important tool for accurate diagnosis. Even in cases not showing one of the recurring alterations, the presence of any clonal cytogenetic abnormality is indicative of a malignant process. Cytogenetic evaluation is also helpful for staging. As disease progresses from a less aggressive to a more acute form, there may be corresponding changes in the karyotype of the malignant cells. Thus in blast crisis CML, it is common to observe cytogenetic abnormalities in addition to the t(9;22). These secondary changes are frequently the first indication that the disease has progressed to a more acute stage. One of the most useful roles for cytogenetic evaluation is for monitoring the outcome of bone marrow transplant. In the case of opposite sex transplant, sex chromosomal differences can serve as markers of patient and donor cells. For same sex transplants, normal heteromorphic differences between patient and donor cells may likewise serve as makers permitting engraftment to be accessed in post-transplant specimens. Whereas cytogenetic analysis is an important diagnostic tool, the eventual successful control of the malignant process will depend upon a better understanding of the molecular events that result from the cytogenetic defects. |