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Structure / Chromosome aberrations
Chromosomes are composed of genes (DNA) that regulate various traits of an organism, such as eye or hair color. Chromosomes are found in the nucleus of a cell. The nucleus might be considered the "brain" of the cell because it is the area that controls the cellís development and function. Chromosome aberrations are any changes in the normal structure or number of chromosomes, often resulting in physical or mental abnormalities. Some of these abnormailities include neoplasia, formation of new tissue; it may even lead to deadly diseases such as cancer. In addition, radiology has played a major part in research on chromosome abnormalities. Many experiments have been done to gain a better understanding of them. Yet, surprisingly, there are actually some "constitutional chromosome aberrations" that are found in each cell of the body. These aberrations are sometimes associated with an increase in the presence of specific kinds of cancer, although the mechanisms of such predispositions are not well understood. For example, deletion of band q14.1 on chromosome 13 is associated with retinoblastoma, a malicious tumor arising in the undifferentiated retina of one or both eyes during infancy or early childhood. Another example is trisomy 21, the presence of three copies of chromosome 21 in the somatic cells of individuals with Down syndrome, is associated with a 1% occurrence rate of leukemia. Also, deletion of band p13 on chromosome 11 is frequently associated with childhood Wilms tumor of the kidney.
Cytogenetic studies over the past few decades have revealed clonal chromosomal aberrations in almost 27,000 human neoplasms. Many of these neoplasia-associated chromosomal abnormalities have been characterized at the molecular level, revealing previously unknown genes that are closely related with the tumorigenic process. The more information gained on chromosome changes in neoplasia, the more difficult it is to identify all recurrent chromosomal aberrations. Recently a computer program has been manufactured to ascertain for the first time all recurrent structural abnormalities in all hematological malignancies and solid tumours published up to June 1996. Out of 26,523 cases, a total of 215 balanced and 1,588 unbalanced recurrent aberrations were identified among 75 different neoplastic disorders.
Other cytogenetic investigations of neoplastic cells during the past 25 years have revealed more than 600 acquired, recurrent, balanced chromosome rearrangements, and it has been established that every tumor type, studied in a sufficient number to permit conclusions, may be subdivided on the basis of specific, and even pathognomonic, abnormalities. At the molecular level, the balanced rearrangements exert their action through one of two alternative mechanisms: deregulation of one gene by relocation to an immunoglobulin or T-cell receptor gene, or the creation of a hybrid gene by the fusion of parts of two genes. As of now, nearly 100 genes have been found to be involved in neoplasia-associated chromosomal rearrangements, the great majority in hematological disorders. Concurrently, the clinical usefulness of various cytogenetic abnormalities as diagnostic and prognostic aids has been increasingly appreciated. The identification of a recurring chromosome abnormality can assist in the diagnosis and subclassification of a malignant disease and, therefore, in the selection of the appropriate treatment. The karyotype is also an independent prognostic factor. In hematological neoplasms, where the knowledge of chromosome abnormalities still is much more complete than is the case with solid tumors, cytogenetic analysis now plays an integral part in the diagnostic work-up of individual patients. Data obtained during recent years strongly suggest that corresponding breakthroughs will be achieved in solid tumors in the near future.
Chromosome aberrations come in two forms: variations in chromosome number and variations in chromosome structure. Various cancers have been associated with both of these types of problems, although the latter seems to be more frequently associated at what may be a causal level. (For more information on the first form, refer to Topic 14: Variations in chromosome number). As for variations in chromosome structure, chromosomal deviations occur with different types of mutations. One of them is deletion, an aberration in which a segment of a chromosome is missing; this may be a segment large enough to be detected under the microscope (macrodeletion) or so small that only sophisticated methods can detect it (microdeletion). Another is duplication, an aberration in which a segment of a chromosome is repeated and thus is present in more than one copy within the chromosome. A third is rearrangement: an aberration in which a segment of a chromosome is shifted within the same chromosome, sometimes turned upside-down (inversion) or transferred to another chromosome; the latter kind of
|Genetic fine structure|
Regulation of gene
Variations in chromosome