Cancer Genetic

Definition:

cancer (malignant tumor) is defined as the abnormal, excessive, uncoordinated, autonomous and purposeless proliferation of cells (in any tissue or organ of the body), which have the tendency to spread & grow in other parts of the body.

Causes & Prevention of Cancer :

Most of the human cancers are caused by certain:
1. chemical.
2.physical
3.biological agents.

The process by which normal cell convert to cancer cell is called malignant transformation.
collectively known as carcinogens.

Role of Heredity:

Familial retinoblastoma, familial adenomatous polyposis, multiple endocrine neoplasia syndrome and hereditary breast & ovarian cancer syndromes.
Members of these families have one or more activated oncogenes in their inherited genome. Therefore fewer additional mutations are required in these persons for the cancer to development.
In most cancers genetic mutations are not inherited and arise in a somatic cells during adulthood as a result of exposure to environmental carcinogens.

In mutations (inherited and acquired) commonly involved three types:
1.Tumor suppressor genes
2.Oncogenes
3.genes involved in DNA repair mechanism.

Tumor suppressor genes:

Retinoblastoma 13 (13q14)

Rb is a tumor suppressor gene. Common in children. Both eyes can be affected. Inherited as an autosomal dominant trait. The gene is located in the proximal long arm of chromosome 13(13q14), where the functional protein of this gene is not absent.

p53

Mutation of the tumor suppressor gene p53 which is located in 17q causes cancer of:
1.Colon cancer
2.Lung cancer
3.Breast cancer
4.Brain cancer
5.Hepatocellular carcinoma
6.Chronic myeloid leukemia in blast crisis.

The most important tumour suppressor genes known so far is:
p53 gene that suppresses uncontrolled proliferation of cells as well as triggers apoptosis (Mutations in p53 gene are seen in about 50 per cent cases of human cancers.
Rb gene (associated with Retinoblastoma and osteo-sarcoma).

Ret gene (associated with Endocrine cancer);
WT-1 (associated with Wilm's tumour);
NF-1 (associated with Neurofibromatosis type-1);
NF-2 (associated with Neurofibromatosis type-2);
APC and DCC (associated with the colon cancer).

Oncogenes:

Cellular oncogenes (c-onc) can be activated to cause cancer as a result of chromosomal rearrangement, e.g. in CML where Ph chromosome can be seen in the malignant bone marrow cells. As a result of this reciprocal translocation of the ABL gene to BCR gene, as a result a novel protein is produced which is said to be the cause of malignancy.


Genes involved in DNA repair mechanisms:

DNA repair mechanisms exist to correct DNA damage due to environmental; mutagens and accidental base misincorporation at the time of DNA replication. Inherited defects in either system can lead to cancer. Example is xerodermal pigmentosum which is an autosomal recessive disorder in DNA repair mechanism after exposure to ultraviolet light.

Cloning, Polymerase Chain Reaction (PCR)

http://www.dnalc.org/ddnalc/resources/animations.html

Cell cycle

The cell cycle, is the series of events that take place in a eukaryotic cell leading to its replication.

The cell cycle consists of four distinct phases: G1 phase, S phase, G2 phase (collectively known as interphase) and M phaseActivation of each phase is dependent on the proper progression and completion of the previous one. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase.

1- M phase

The relatively brief M phase consists of nuclear division (karyokinesis) and cytoplasmic division (cytokinesis). In plants and algae, cytokinesis is accompanied by the formation of a new cell wall. The M phase has been broken down into several distinct phases, sequentially known as prophase, prometaphase, metaphase, anaphase and telophase leading to cytokinesis.

2- Interphase

After M phase, the daughter cells each begin interphase of a new cycle. Although the various stages of interphase are not usually morphologically distinguishable, each phase of the cell cycle has a distinct set of specialized biochemical processes that prepare the cell for initiation of cell division.

a. G1 phase
The first phase within interphase, from the end of the previous M phase till the beginning of DNA synthesis is called G1 (G indicating gap or growth). During this phase the biosynthetic activities of the cell, which had been considerably slowed down during M phase, resume at a high rate. This phase is marked by synthesis of various enzymes that are required in S phase, mainly those needed for DNA replication. Duration of G1 is highly variable, even among different cells of the same species.

b. S phase
The ensuing S phase starts when DNA synthesis commences; when it is complete, all of the chromosomes have been replicated, i.e., each chromosome has two (sister) chromatids. Thus, during this phase, the amount of DNA in the cell has effectively doubled.

c. G2 phase
The cell then enters the G2phase, which lasts until the cell enters mitosis. Again, significant protein synthesis occurs during this phase, mainly involving the production of microtubules, which are required during the process of mitosis. Inhibition of protein synthesis during G2 phase prevents the cell from undergoing mitosis.

Referances:-

homepage.mac.com/enognog/checkpoint.htm

http://en.wikipedia.org/wiki/Cell_cycle

Breast cancer

For those who are working in breast cancer project, go to this web site:
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=genetics&rid=cmed6.section.30813#30819

Mendel’s Principles of Inheritance

Inherited traits are transmitted by genes which occur in alternate forms called alleles

• Principle of Dominance - when 2 forms of the same gene are present the dominant allele is expressed
• Principle of Segregation - in meiosis two alleles separate so that each gamete receives only one form of the gene
• Principle of Independent Assortment - each trait is inherited independent of other traits (chance)
  

Mendel laws

Gregor Mendel studied the garden pea height, flower color, seed coat color, and seed shape over many generations. He chose 1 or 2 traits per generation to watch acrossed plants with different traits and learned that offspring usually had dominate trait.

No matter what trait he selected for the second generation would show traits at a ratio of 3 to 1 (3 dominat

Mendel found that the inheritance of traits was not due to blending but instead specific traits or units of inheritance were passed from generation to generation we call those units of inheritance genes.

Non-genetic sex-determination systems

Many other sex-determination systems exist. In some species of reptiles, including alligators, some turtles, and the tuatara, sex is determined by the temperature at which the egg is incubated. Other species, such as some snails, practice sex change: adults start out male, then become female. In tropical clown fish, the dominant individual in a group becomes female while the other ones are male.
Some species have no sex-determination system. Earthworms and some snails hermaphrodites; a few species of lizard, fish, and insect are all female and reproduce by parthenogenesis.
In some arthropods, sex is determined by infection, as when Bacteria of the genus Wolbachia alter their sexuality; some species consist entirely of ZZ individuals, with sex determined by the presence of Wolbachia.

Reference:

http://en.wikipedia.org/wiki/Sex-determination_system