Sei sulla pagina 1di 3

Oncology tutorial:

2. There are two main classes of cancer genes which are oncogenes and tumor
suppressor genes. A third class, a subtype of tumor suppressor genes called the caretaker
genes, is now recognized. Mutations in cancer genes can be inherited but, in the majority
of cases, they occur during a persons lifetime. Oncogenes cause normal cells to grow out
of control and become cancer cells. They are mutated forms of normal genes called protooncogenes. Proto-oncogenes normally control how often a cell divides and the degree to
which it differentiates. When a proto-oncogene mutates into an oncogene, usually
through amplification, translocation or point mutation, it becomes permanently turned
on or activated when it is not supposed to be. When this occurs, the cell divides too
quickly, which can lead to cancer. Only one of the two alleles of a proto-oncogene needs
to be overactive in order to have an oncogenic effect. An example of an oncogene is
BCR-ABL. This is formed by a translocation between sections of human chromosomes 9
and 22, resulting in what is known as the Philadelphia chromosome. The resulting BcrAbl protein interferes with signalling pathways within cells and causes the overproduction of white blood cells, leading to chronic myeloid leukaemia (CML). As the
Bcr-Abl fusion protein is unique to leukaemic cells it presents a potential target for
Tumour suppressor genes encode proteins that normally slow down cell division,
repair DNA mistakes, and trigger apoptosis. Inactivation of tumour suppressor genes can
lead to cells growing out of control, which can lead to cancer. Inactivation can occur
through point mutation, deletion or epigenetic mechanisms. While most oncogenes
develop from mutations acquired during the life of the individual, mutations of tumour
suppressor genes can be inherited as well as acquired. The TP53 gene, is the most
frequently inactivated gene in human cancers. It normally encodes a pivotal transcription
factor that puts a brake on abnormal cell growth and triggers apoptosis in cells that have
sustained DNA damage. Originally, it was believed that both alleles of a tumour
suppressor gene must be mutated in order to render it inactive. This two-hit model of
tumour suppressor inactivation has provided a useful conceptual framework for research
on the genetics and biology of tumour suppressor genes.

But more recently some

evidence has emerged that mutations in tumour suppressor genes are not always
completely recessive; some tumour suppressor genes need only one allele to be mutated
to produce an oncogenic effect. These single allele mutations can act by producing a
dominant-negative protein (a protein whose abnormal function overpowers that of the
normal protein), or by altering the total amount of protein produced.
Caretaker genes are a class of tumour suppressor genes but, as they do not
regulate cell division, their inactivation is not directly responsible for cancer
development. Many caretaker genes, also known as stability genes, are involved in
recognising and repairing DNA damage. Their inactivation causes genetic instability and
leads to increases in the mutation rate of all genes, including oncogenes and tumour
suppressor genes.
The development of cancer requires the accumulation of mutations in a number of
key genes. Different tissues and types of cells will require different combinations of
genes to be mutated in order to become cancerous. A study of breast and colorectal
cancer cell lines has shown that these cancer cells may harbour an average of around 90
mutant genes. But only a few of these mutations will actually be responsible for the
development of the cancer. For example, some scientists have estimated that a minimum
of five genetic alterations is needed for the development of colon cancer. The other
mutations are known as bystander or passenger mutations and confer neither a growth
advantage nor disadvantage. They are especially common in tumours in which caretaker
genes are mutated. In sporadic cases of cancer, the initial genetic alteration occurs in a
single cell. If this is not repaired, it is passed to daughter cells during cell division. If one
of these daughter cells acquires a further genetic alteration(s), it passes this and the
original alteration on to its daughter cells. If this process is repeated a number of times,
populations of increasingly abnormal cells are formed. Eventually, this leads to the
development of a cancer capable of invasion and spread. Although historically the initial
genetic alteration was thought to occur in a differentiated cell, increasingly, scientists
believe that cancers actually arise from stem cells.

3. Cancer is a genetic disease results from increased activity of the cell cycle, decreased
activity of the cell differentiation pathway, decreased DNA repair, and decreased cell
death. To achieve higher proliferation and survival rates, they undergo mutations in
critical pathways that counterbalance the negative apoptotic balance, thus becoming
optimal candidates for selection in contests of "survival of the fittest." Mutations
affecting apoptosis genes, growth controlling genes, and survival genes such as PTEN
can in fact often be found in malignant cells.