The Types of Cancer - Case Study Example

Chromosomal Rearrangements Describe how chromosomal rearrangements can lead to cancer.  Cancer is the abnormal production of the cells of an organism which are proliferated in an uncontrolled way and sometimes spread. Cancer is commonly used for all types of malignant tumors, which is the swelling of any tissue of the body caused by inflammation, which are studied in Oncology. Neoplasm is defined by a British oncologist Willis as “Abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissue and persists in the same excessive manner after cessation of the stimuli which evoked the change.”(Willis 5). The types of cancer are more than 100 because there are more than 100 different types of cells in the body of an organism, for example skin cancer, lungs cancer, prostate cancer and breast cancer etc (Robbins et al 2005). Under microscope, cancer cells show different structural characteristics because of which they can be differentiated from the normal cells. They are pleomorphic in nature, which means that they have a tendency to have a variable size and shape than the normal cells. The cancer cells have different size and different shapes. Most of the cancer cells have large nuclei from the surrounding normal tissue cells and the nuclei of the cancerous cells contain abnormal number of chromosomes, a condition known as aneuploidy. The aneuploidy may occur due to mutation or deletion of chromosome or any other reason. The cell membrane of the cancer cells produces some sort of surface enzymes which have the ability to damage the basement membrane of tissues, with the help of which the cancer spreads more easily to the surrounding non-cancerous cells and damages them too. The cancer cells show increased rate of mitosis, which is the process of the reproduction of the new cells and hence the cancer spreads to the surroundings. The cancer cells have differences in metabolism in comparison to normal cells, as their metabolism is more anaerobic and therefore they may even combat hypoxic conditions. (Trahan 2001 & Robbins et al 2005) Chromosomal rearrangements have been found to be existing in many forms of cancers such as leukumias and lymhpomas. It is believed that chromosomal instability is a great cause for the onset of a certain type of cancer. Chromosomal rearrangements are believed to have an effect on the protooncogenes. Translocation and inversion of a chromosome in particular have significant effect on the protooncogenes. Translocation is particularly important when studying about the chromosomal rearrangements leading to cancer. Translocations have two ways through which they can activate the protoncogenes one in which the overexpression of protooncogenes takes place which happens after the removal of these genes from the elements which hold them. Secondly these translocations in many tumors form hybrid genes by combining two sets of different genes together. These hybrid genes can then enhance the production of chimeric proteins. The overexpression of a protooncogene by these chromosomal translocations can be viewed in the lymphomas of Burkitt. It is seen that in most of these lymphomas one or more translocations at specific chromosomes occur. The chromosome involved in this lymphoma is usually the 8q24 chromosome along with a chromosome which carries the immunoglobulin gene. In these lymphomas it is seen that the translocation causes mutations and irregular sequence in the MYC gene. This then causes the cancer to arise in individuals with this kind of mutation. Similarly another example of chromosomal abnormality is also seen in the case of myeloid leukemia. This situation is also called the Philadelphia chromosome in which separate sequences of genes fuse together to form an oncogene. In most of the cases it is seen that the translocation occurs at chromosomes 9 and 22. The oncogene that is produced by this translocation is known as BCR-ABL which produces a sequence for a chimeric protein. This chimeric protein has several enzymes in it which possess tyrosine kinase activity. (Kurzrock et al 2003).It is believed that this oncogene has an impact on the metabolic processes of different cells. Apoptosis is believed to be inhibited by this oncogene as a result of chromosomal translocation. Similarly cell adhesion and DNA repair impairment is also believed to cause the onset of the cancer in this translocation. It is believed that gene fusions also occur because of some factors which take part in transcription (Sattler & Griffin 2003). Deletions in chromosomes can also have effects on the cancer cells. Deletion in chromosomes at points where they contain the tumor suppressor genes can cause the tumor to proliferate and form cells which are unwanted. These tumor suppressor cells help to regulate the cells in the body so that cancer can be avoided. These tumor suppressor genes are necessary for the production of tumor suppressor proteins. One example of deletion in chromosome can cause eye cancer known as retinoblastoma. Chromosome 13 consists the necessary genes required to produce the tumor suppressor proteins and if this is disrupted the cancer of eye would occur (Robbins et al 2005). Inversion is a less likely chromosomal disability because of which cancers can occur. Inversion however can have profound effects on the formation of cancer cells. It is believed that inversion can cause the cells to proliferate rapidly and activate the oncogenes. These inversions can also cause the formation of a fusion gene. An example of inversion in real life can be seen in the inversion of chromosome ten. This inversion on chromosome ten can cause the proto-oncogene to combine with another gene to form an oncogene. An oncogene can trigger carcinogenesis and cause the production of other cells. Such an inversion is usually seen in thyroid cells because of which the cancer of thyroid can occur (Robbins et al 2005). Chromosome abnormalities have a profound effect on the growth of cancer in an individual. Chromosomal abnormalities are mostly hereditary and at times the environmental factors also influence these chromosomal abnormalities. Further research is however required to clarify as to why these abnormalities really do occur and in what way can these abnormalities be prevented. Describe the FOUR main types of structural chromosomal abnormality and the mechanisms by which they can arise [40%]. Use examples to illustrate the consequences of such rearrangements both on the individual in whom the rearrangement arose and, where appropriate, on their offspring [60% Structural chromosomal abnormalities arise when different enzymes are not able to repair several breaks in the pattern of chromosomes or even if they are able to do so these repairs are not specific enough to avoid the abnormality. These can be caused by chemicals, radiations, viruses, or any other type of abnormal event. These structural abnormalities are classified into four main classes respectively. These are Deletions, Translocations, Inversions and Ring Chromosome (Sadler 2009; Robbins et al 2005). Deletions Deletions occur when a specific chromosome loses its segment and is then termed to irreparable even with the enzymes. These deletions are of two types i.e. terminal deletions or interstitial deletions. Terminal deletions are the ones in which one end of a chromosome loses its segment whereas the interstitial deletions are the ones in which the chromosome loses its segment from the middle most portion. This usually causes partial monosomy to occur in the chromosomes and can lead to many disease conditions. Some of the conditions which result because of deletions are DiGeorge Syndrome, Angelman Syndrome and Prader-Willi Syndrome. If the deletion of a gene which maps to chromosome 22q11 occurs DiGeorge Syndrome will possibly occur. (Epstein 2001). The gene which is mutated in this syndrome is responsible for transcription factors of the T-family which help in the development of branchial arch and the great vessels. Patients suffering from the syndrome have undeveloped third and fourth pharyngeal pouches. Fourth pharyngeal pouch forms the thymus and because of this thymus is not formed in these patients which lead to T-cell deficiency. Thus these patients have a poor defense against various bacterias and fungal infections. Angelman Syndrome is believed to be caused by an interstitial deletion of a band in the long arm of chromosome 15. The patients would inherit this chromosomal defect from their mothers because of which they would suffer from mental retardation and cat like laughter. (Smith & Laan 2003). It is necessary that this defect is inherited from the maternal gene as if it is from the paternal side Prader-Willi Syndrome may occur. The children with Angelman Syndrome show poor motor development alongside with the mental retardation. Prader-Willi Syndrome on the other hand is caused by a deletion of a gene in the paternal side. This deletion is again on the same band of chromosome 15 in the paternal genes. Patients suffering from Prader-Willi Syndrome show signs of mental retardation, lack of growth, hyptonia, hypogonadism and obesity (Nicholls & Knepper 2001). Inversions Inversions occur when chromosomes are of the same composition but their arrangement gets different. In other words the bonding of chromosomes is of incorrect pairing which leads to inversion. Inversions are of two types i.e. paracentric and pericentric respectively. An inversion is called paracentric when the centromere of the chromosome is outside the region of inversion whereas pericentric inversion is the one in which the centromere is located inside the region of inversion. It is believed that these inversions do not cause much of a distortion to the normal development of a child. However these inversions can cause unusual gametes to be formed which may result in imbalanced fertilization (Robbins et al 2005). Translocation Translocations occur when a whole segment of chromosome is exchanged with another chromosome. Two types of translocations are known as reciprocal translocations and Robertosonian translocations. Reciprocal Translocation occurs when exchange of segments occur between nonhomologous pairs of chromosomes. This type of translocation usually does not cause any abnormality but in some cases it can case myelogenous leukemia may occur. However individuals with such a chromosome may have difficulties during fertilization as abnormal gametes may be formed because of the unusual sequence of genes. Some of the cases also show malformed birth because of these abnormal gametes. Robertosonian translocations are the ones which occur between two acrocentric chromosomes. These two acrocentric chromosomes break near the centromere and get joined in a similar fashion such that p arm of the chromosome is lost. Such type of translocations can have a profound effect on the individual and the offsprings too. The individuals can suffer from Trisomy 13 which is also called Downs Syndrome. Individuals with such a translocation experience a lot of abortions because of monosomic and trisomic embryos. It occurs because of nondisjunction of the genes in an individual which is usually seen in the chromosome 21. Individuals with Downs Syndrome show mental retardation, heart defects such as defects of endocardial cushions or ventricular septal defects, leukemia, degeneration of nervous tissue, and abnormal immune responses (Ugazio et al 1990; Robbins et al 2005). The patients suffering from this disorder also show flat facial profile, epicanthic folds umbilical hernia and hyptonia. Ring Chromosome Ring Chromosome is a form of deletion in which ends of chromosomes fuse together to make it up for the damaged segments. Usually it is seen that no genetic material is lost in the formation of a ring chromosome but in some cases this material is lost and an abnormality occurs. Turners Syndrome is an example of chromosomal ring formation. Turners Syndrome is usually seen in women and results from defects in the X chromosome. The deletions of long or short arms of a chromosome can cause the ring structure to be formed. These patients show signs of edema in infancy with resultant cystic hygroma in some patients. It is also a leading cause of heart disease in these patients which particularly occurs because of coartcation of aorta or defects in the aortic valve. Patients suffering from Turners Syndrome normally are not able to develop sexual characteristics even at the age of puberty. Amenorrhea is also seen in these patients along with hypothyroidism. As the X chromosome is absent in these individuals it is seen that a great number of oocytes are lost by these patient at the age of puberty because of which they are not able develop the sexual characteristics. Other signs of Turners Syndrome seen in patient are infertilitization, pigmented nevi, short stature, cubitis valgus and streak ovaries (Robbins et al 2005). All these chromosomal abnormalities together are seen in patients due to different reasons. The possible causes of structural aberrations in chromosomes are because of radiation, chemicals or any other event. Further research is being carried out to find different molecular mechanisms of these diseases so that it can be established as to how these chromosomal abnormalities can be prevented. Bibliography Willis, Rupert Allan. The Spread of Tumors in the Human Body. London: Butterworths, 1952.Bottom of Form Kumar, Vinay, Abul K. Abbas, Nelson Fausto, Stanley L. Robbins, and Ramzi S. Cotran. Robbins and Cotran Pathologic Basis of Disease. Philadelphia: Elsevier Saunders, 2005. Rieger, Paula Trahan. Biotherapy A Comprehensive Overview (Jones and Bartlett Series in Oncology). New York: Jones & Bartlett, 2001. Print. Top of Form Kurzrock, R., H. M. Kantarjian, B. J. Druker, and M. Talpaz. "Philadelphia Chromosome-Positive Leukemias: From Basic Mechanisms to Molecular Therapeutics." ANNALS OF INTERNAL MEDICINE. 138 (2003): 819-830. Top of Form Sattler, Martin, and James D Griffin. 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