cancer and chromosomes

Cancer, Chromosomes and Genes : 

Cancer, Chromosomes and Genes Dr. R. K Pillai Dept of Zoology Hindu College Moradabad – 244 001

CancerIntroduction : 

CancerIntroduction Cancerous tumours kill several hundred thousand of people every year. Many cancers result from genetic malfunctions such as chromosomal and gene mutations. These malfunctions may be triggered by environmental factors such as: diet excessive exposure to sunlight chemical pollutants. Cancers arise when critical genes are mutated. These mutations can cause biochemical processes to go abnormal and lead to the unregulated proliferation or multiplication of cells. Without regulation, cancer cells divide forming tumours. When cells detach from a tumour and invade the surrounding tissues, the tumour is malignant.

What is cancer? : 

What is cancer? Cancer is not a single disease, but rather a group of diseases. Cancers can originate in many different tissues of the body. A number of human tumours have been shown to be associated with chromosomal mutations. It can be through a change in number of chromosomes through nondisjunction. It can be through a change in chromosome structure involving deletions, duplications, inversions and translocations. It is not clear whether the tumour is caused by chromosomal mutation, or whether the chromosomal mutation results from the growth activities of the tumour cell. Two examples of tumours associated with chromosome translocations are chronic myelogenous leukaemia (CML) and Burkitt's lymphoma.

1. Chronic Myelogenous Leukaemia (CML) : 

1. Chronic Myelogenous Leukaemia (CML) CML is a fatal cancer involving uncontrolled replication of myeloblasts (stem cells of white blood cells). Ninety percent of CML is associated with an aberration of chromosome 22. This abnormal chromosome was originally discovered in the city of Philadelphia and thus is called the 'Philadelphia chromosome'. Initially it was thought to have a simple deletion in its long arm. Subsequent analysis using molecular techniques has shown that the Philadelphia chromosome is actually the result of a reciprocal translocation between chromosomes 9 and 22.

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Reciprocal translocation involved in the Philadelphia chromosome associated with chronic myelogenous leukaemia

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In the Philadelphia translocation, the tip of the long arm of chromosome 9 has been joined to the body of chromosome 22. The distal portion of the long arm of chromosome 22 has been joined to the body of chromosome 9 . The translocation breakpoint on chromosome 9 is in the c-abl ( cellular Abelson) oncogene, which encodes a tyrosine kinase, and the breakpoint on chromosome 22 is in a gene called bcr (breakpoint cluster region). Through the translocation, the bcr and c-abl genes have been physically joined, creating a fusion gene whose polypeptide product has the amino terminus of the bcr protein and the carboxy terminus of the abl protein. It is not understood precisely why, this fusion polypeptide causes white blood cells to become cancerous.

2. Burkitt’s lymphoma : 

2. Burkitt’s lymphoma Burkitt’s lymphoma, a particularly common disease in Africa. It is another example of a white blood cell cancer associated with reciprocal translocations. These translocations invariably involve chromosome 8 and one of the three chromosomes (2, 14, and 22) that carry genes encoding the polypeptides that form immunoglobulins or antibodies .

Reciprocal translocation involved in Burkitt's lymphoma : 

Reciprocal translocation involved in Burkitt's lymphoma Translocations involving chromosomes 8 and 14 are the most common . In these translocations, the c-myc (c-mick) oncogene on chromosome 8 is juxtaposed to the genes for the immunoglobulin heavy chains on chromosome 14. This rearrangement results in the overexpression of the c- myc oncogene in cells that produce immunoglobulin heavy chains-that is, in B lymphocytes - and this overexpression causes those cells to become cancerous.

3. Wilms' tumour : 

3. Wilms' tumour Wilms' tumour is the most common form of kidney cancer in children. It is also called nephroblastoma. "Nephro" means kidney, and a "blastoma" is a tumour made of embryonic tissue that has not yet fully developed. Wilms' tumour was named after a German surgeon, Max Wilms, who published the first detailed description of the disease in 1899. The causes of all Wilms' tumor are not known.

Max Wilms : 

Max Wilms In the majority of cases, the genetic changes occur only in the kidney cells and not in other cells of the body Mutations of the WT1 gene on chromosome 11 p 13 are observed in approximately 20% of Wilms' tumors. However, some of these tumors appear to result from changes in one or more of several genes. At least half of the Wilms' tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin. A gene on the X chromosome, WTX, is inactivated in up to 30% of Wilms' tumor cases.

4. Retinoblastoma : 

4. Retinoblastoma This form of cancer develops in the retina, which is the specialized light-sensitive tissue at the back of the eye that detects light and color. In most children with retinoblastoma, the disease affects only one eye. However, one out of three children with retinoblastoma develops cancer in both eyes. The most common first sign of retinoblastoma is a visible whiteness in the pupil called "cat's eye reflex" or leukocoria.

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Retinoblastoma is caused by abnormalities of a gene called RB1, which is located on a region of the long (q) arm of chromosome 13 designated 13q14. Although most retinoblastomas are caused by mutations within the RB1 gene, a small percentage of retinoblastomas result from a deletion of the 13q14 region. In addition to retinoblastoma, deletions of the 13q14 region may cause intellectual disability, slow growth, and characteristic facial features such as prominent eyebrows, a broad nasal bridge, a short nose, and ear abnormalities. A loss of several genes is likely responsible for these developmental problems, although researchers have not determined which other genes in the deleted region are involved. Retinoblastoma is a rare type of eye cancer that usually develops in early childhood, typically before the age of 5.