How does chromosomal translocation cause cancer?
Chromosomal translocations are favored in neighboring chromosomes or genes in spatial proximity within the nucleus. Chromosomal translocations leading to cancer are generally via two ways, formation of oncogenic fusion protein or oncogene activation by a new promoter or enhancer.
How does the Philadelphia chromosome cause cancer?
The Philadelphia chromosome is only found in the affected blood cells. Because of the damage to the DNA, the Philadelphia chromosome results in the production of an abnormal enzyme called a tyrosine kinase. Along with other abnormalities, this enzyme causes the cancer cell to grow uncontrollably.
How can translocation occur as the result of the onset or causing a disease like cancer?
A translocation is a type of abnormal change in the structure of a chromosome that occurs when a part of one chromosome breaks off and sticks to another chromosome. These “mutations” are an important cause of many types of lymphomas and leukemias.
What is the effect of translocation mutation?
However, carriers of balanced reciprocal translocations have increased risks of creating gametes with unbalanced chromosome translocations, leading to Infertility, miscarriages or children with abnormalities. Genetic counseling and genetic testing are often offered to families that may carry a translocation.
How can a chromosomal translocation cause a disease?
Depending on the chromosome breakpoints, a translocation can result in the disruption or misregulation of normal gene function. These molecular rearrangements, in many cases, are considered to be the primary cause of various cancers.
Why does translocation occur?
Translocations occur when chromosomes become broken during meiosis and the resulting fragment becomes joined to another chromosome. Provided that there is no loss of genetic material, the translocation is balanced (i.e. no loss or gain of genetic material) and usually results in normal development.
Can Philadelphia chromosome be cured?
In pediatric patients with acute lymphoblastic leukemia (ALL), the Philadelphia chromosome translocation is uncommon, with a frequency of less than 5%. However, it is classified as a high or very high risk, and only 20-30% of Philadelphia chromosome-positive (Ph+) children with ALL are cured with chemotherapy alone.
What are the symptoms of Philadelphia chromosome?
When they occur, signs and symptoms may include:
- Bone pain.
- Easy bleeding.
- Feeling full after eating a small amount of food.
- Feeling run-down or tired.
- Weight loss without trying.
- Loss of appetite.
- Pain or fullness below the ribs on the left side.
What does the Philadelphia chromosome do?
The Philadelphia chromosome forms when chromosome 9 and chromosome 22 break and exchange portions. This creates an abnormally small chromosome 22 and a new combination of instructions for your cells that can lead to the development of chronic myelogenous leukemia.
What disease is caused by deletion mutation?
Deletions are responsible for an array of genetic disorders, including some cases of male infertility, two thirds of cases of Duchenne muscular dystrophy, and two thirds of cases of cystic fibrosis (those caused by ΔF508).
What are the types of translocation?
There are two main types of translocations: reciprocal and Robertsonian. In a reciprocal translocation, two different chromosomes have exchanged segments with each other. In a Robertsonian translocation, an entire chromosome attaches to another at the centromere.
What causes chromosomes to break?
Chromosome breakage caused by the presence of a DSB leads to an uneven distribution of chromosomes over the daughter cells during mitosis, resulting in deletion or translocation of potentially critical genes, such as oncogenes or tumor suppressor genes.
How do you know if translocation is balanced?
Balanced translocation errors are diagnosed through karyotyping. Blood samples are collected from each parent and analyzed for translocation.
What causes translocation mutation?
Translocations. A translocation occurs when a piece of one chromosome breaks off and attaches to another chromosome. This type of rearrangement is described as balanced if no genetic material is gained or lost in the cell. If there is a gain or loss of genetic material, the translocation is described as unbalanced.
What are the reproductive consequences of a balanced translocation?
Balanced chromosomal translocations may cause the loss of genetic material at breakpoints and may result in failure of spermatogenesis . Individuals affected by such translocations exhibit reproductive problems such as infertility, recurrent pregnancy loss, and malformed offspring [4, 5].