A chromosome is a single long strand of DNA that is wound up and bunched together into a compact structure. (Human chromosomes are depicted in figure to the left.) A gene is a segment of DNA on a chromosome and is the basic unit of heredity, directing the development and maintenance of cells and the organism.
When a human cell is preparing to divide, it copies each of its 23 pairs of chromosomes so that each new cell can receive a complete set. Occasionally, a strand of DNA will break during this process. The cell usually repairs these fractures correctly. If it cannot be fixed, the cell will induce programmed cell death, or apoptosis.
However, on occasion a cell will incorrectly join two or more different chromosomes, yielding what is called a translocation. If the cell subsequently escapes its own destruction, the new cells can inherit an incorrect number of copies of that piece of chromosome. Furthermore, if the DNA is snapped and incorrectly repaired in a region that specifies a gene, that valuable piece of the genetic code may be damaged, leaving the cell with only one remaining copy on the unbroken partner in the chromosome pair. Another possibility is that the improperly repaired DNA will encode a "fusion protein," made from the sequences of two different genes spliced together. Many fusion proteins are harmless and merely ineffective, but some can have detrimental effects. If the original gene – the one damaged – carried out a vital function in the cell, such as regulating cell division, the fusion protein can cause big problems.
These breaking-and-joining events do not happen randomly, and certain translocations can lead to specific kinds of cancer. For instance, when an extra copy of the long arm of chromosome 12 is inherited, this may lead to liposarcoma. With two normal copies of chromosome 12 plus the extra fragment, cells manufacture too much of the protein encoded by one of the resident genes: the cyclin-dependent kinase 4 gene, known commonly as CDK4. The CDK4 protein is a kinase, meaning it is an enzyme that adds phosphate groups onto other proteins to activate or inactivate them. CDK4 acts on retinoblastoma tumor suppressor, or RB, which helps control cell division. When there is too much CDK4 (as happens when it inherits excess copies of the gene), this causes RB to have an excessive number of phosphate groups, thereby heightening the rate of cell-division, a trademark characteristic of cancer.
There are several other characteristic translocations and resultant fusion proteins that have been discovered that may lead to developing certain subtypes of sarcoma. Several are listed in the table below.
They are listed in a specific format that is indicated below:
abn abbrev (first chrom; second chrom) (arm band location/number; arm band location/number)
abn abbrev: The aberration abbreviation, AKA the chromosomal abnormality type. This could be a chromosomal translocation (t), deletion (del), duplication (dup), etc.
first chrom: The first chromosome involved in the abnormality
Second chrom: The second chromosome involved
Arm band location/number: This is a description of the location on a chromosome arm, in order from the centromere out to the end of the chromosome. The letter q indicates the abnormality involves the long arm of the chromosome. The letter p indicates the short arm. These numbers are a standard determined by the International System for human Cytogenetic nomenclature (ISCN), revised in 2005.