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The ALK gene (ALK stands for Anaplastic Lymphoma Kinase) encodes a protein that is located on the cell surface and belongs to a family of receptor tyrosine kinases (RTKs). RTKs are the first link in a chain that sends signals from the outside of a cell to the signal cascades inside the cell that control different cellular processes, such as cell growth, cell division and cell differentiation.
ALK is believed to play a role in brain development and helps to regulate the proliferation of nerve cells during early stages of development. In several types of cancer, the ALK gene has been found to be genetically altered, and these alterations result in abnormal ALK proteins that cannot be normally regulated by the cell.
Many types of genetic alterations in the ALK gene have been found in different cancers. Some cancers contain ALK genes that have genetic mutations, or changes in the nucleotide sequence in the ALK gene. Other types of cancers have been found to have amplified ALK, meaning that many copies of the ALK gene have been added to the DNA. This leads to a higher level of the ALK protein in tumor cells, overwhelming the cells normal ability to regulate the ALK protein. Another type of genetic alteration in the ALK gene that is found in cancer is called gene fusions or gene rearrangements. This is the result of an event where a portion of the ALK gene breaks away from its normal location on the DNA, and inserts itself into a different gene in another location. The protein that results from this event is a fusion protein-part ALK, and part of another protein. The gene-fusions found in cancer are activated, and like the mutations and amplifications described above, send continual signals to the cell to grow and divide, resulting in cancer.
Source: Genetics Home Reference
ALK is a gene that provides the code for making a protein called anaplastic lymphoma kinase. This protein belongs to a family of proteins on the cell surface known as receptor tyrosine kinases (RTKs). RTKs are the first link in a chain that sends signals from the outside of a cell to the parts inside the cell that control different cellular processes, such as cell growth, cell division and cell differentiation. Anaplastic lymphoma kinase is believed to play a key role in brain development and helps regulate the proliferation of nerve cells during early stages of development. In cancer, either due to mutation or rearrangements in the ALK gene, its activity is continuously switched on, which in turn drives the cancer process.
At least 16 mutations in the ALK gene have been found in some patients with neuroblastoma, a cancer that develops in the immature nerve cells (neuroblasts) during childhood. In most cases, each mutation alters the structure of the ALK protein in different ways. These mutations result in the signaling pathway being switched on, increasing the proliferation of immature nerve cells and leading to neuroblastoma. Some of these mutations are inherited and some are called somatic because they are acquired during the course of a person's life and are found only in cells that become cancerous (not inherited from a parent). In some people with neuroblastoma, extra copies (gene amplification) of ALK cause too much protein to be made.
Rearrangements in the ALK gene also serve as an important driver of tumor growth. These rearrangements result in the production of a recombinant protein that is comprised of the front end of one protein fused together with the tyrosine kinase domain of ALK. The fusion partner can be any one of a number of genes, depending on the malignancy. For instance, in approximately 70 to 80% of ALK-positive anaplastic large cell lymphomas (ALCL), ALK is paired with the Nucleophosmin (NPM) gene. In lung cancer, ALK's translocation partner is primarily the EML4 gene. ALK rearrangements have also been described in other tumors including inflammatory myofibroblastic tumors, neural tumors, rhabdomyosarcomas and in some subtypes of breast cancer. Another type of rearrangement, an inversion, is found in a few people with non-small cell lung cancer (NSCLC), the most common type of lung cancer.
Source: Genetics Home Reference