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Genetics Home Reference: your guide to understanding genetic conditions
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ALK

Reviewed March 2011

What is the official name of the ALK gene?

The official name of this gene is “anaplastic lymphoma receptor tyrosine kinase.”

ALK is the gene's official symbol. The ALK gene is also known by other names, listed below.

What is the normal function of the ALK gene?

The ALK gene provides instructions for making a protein called anaplastic lymphoma kinase, part of a family of proteins called receptor tyrosine kinases (RTKs). Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The process begins when the kinase is stimulated at the cell surface and then attaches to a similar kinase (dimerizes). After dimerization, the kinase is tagged with a marker called a phosphate group (a cluster of oxygen and phosphorus atoms) in a process called phosphorylation. Phosphorylation turns on (activates) the kinase. The activated kinase is able to transfer a phosphate group to another protein inside the cell, which is activated as a result. The activation continues through a series of proteins in a signaling pathway. These signaling pathways are important in many cellular processes such as cell growth and division (proliferation) or maturation (differentiation).

Although the specific function of anaplastic lymphoma kinase is unknown, it is thought to act early in development to help regulate the proliferation of nerve cells.

Does the ALK gene share characteristics with other genes?

The ALK gene belongs to a family of genes called CD (CD molecules).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the ALK gene related to health conditions?

neuroblastoma - increased risk from variations of the ALK gene

At least 16 mutations in the ALK gene have been identified in some people with neuroblastoma, a type of cancerous tumor composed of immature nerve cells (neuroblasts). Neuroblastoma and other cancers occur when a buildup of genetic mutations in critical genes—those that control cell proliferation or differentiation—allows cells to grow and divide uncontrollably to form a tumor. In most cases, these genetic changes are acquired during a person's lifetime and are called somatic mutations. Somatic mutations are present only in certain cells and are not inherited. Less commonly, gene mutations that increase the risk of developing cancer can be inherited from a parent. Both types of mutation occur in neuroblastoma. Somatic mutations in the ALK gene occur during the development of some cases of sporadic neuroblastoma, and inherited mutations in the ALK gene increase the risk of developing familial neuroblastoma.

Mutations in the ALK gene change single protein building blocks (amino acids) in anaplastic lymphoma kinase. The most common mutation in neuroblastoma replaces the amino acid arginine with the amino acid glutamine at position 1275 (written as Arg1275Gln or R1275Q). Arg1275Gln has been found in both familial and sporadic neuroblastoma and is the only common ALK gene mutation that has been found in both types of the condition.

Occasionally, extra copies of the ALK gene are found in people with neuroblastoma. This phenomenon, known as gene amplification, results in overexpression of anaplastic lymphoma kinase.

Mutated or overexpressed anaplastic lymphoma kinase no longer requires stimulation from outside the cell to be phosphorylated. As a result, the kinase and the downstream signaling pathway are constantly turned on (constitutively activated). Constitutive activation of anaplastic lymphoma kinase may increase the proliferation of immature nerve cells, leading to neuroblastoma.

other cancers - increased risk from variations of the ALK gene

Rearrangements of genetic material involving the ALK gene on chromosome 2 increase the risk of developing several other types of cancer. These rearrangements are somatic mutations, which means they occur during a person's lifetime and are present only in the cells that become cancerous.

One type of rearrangement, called a translocation, exchanges genetic material between chromosome 2 and another chromosome. At least 15 translocations involving the ALK gene have been identified in people with anaplastic large cell lymphoma (ALCL), a rare form of cancer involving immune cells called T cells. The most common translocation in ALCL occurs between chromosome 2 and chromosome 5, called t(2;5). This translocation fuses the ALK gene to the NPM gene and results in a fusion protein called NPM-ALK. In addition, at least seven translocations involving the ALK gene have been identified in inflammatory myofibroblastic tumor (IMT). IMT is a rare cancer characterized by a solid tumor composed of inflammatory cells and cells called myofibroblasts that are important in wound healing. About half of people with IMT have a translocation involving the ALK gene.

Another type of rearrangement, called an inversion, occurs when chromosome 2 is broken in two places and the resulting piece of DNA is reversed and re-inserted into the chromosome. A small group of people with non-small cell lung cancer, the most common type of lung cancer, have an inversion of chromosome 2. This inversion fuses the ALK gene with another gene called EML4 and results in the EML4-ALK fusion protein.

The fusion proteins created by these rearranged genes have functions of both anaplastic lymphoma kinase and the partner protein. The presence of the partner protein allows phosphorylation of anaplastic lymphoma kinase without dimerization. The fusion protein and signaling pathways activated by anaplastic lymphoma kinase are constitutively activated, which may abnormally increase the proliferation of immature nerve cells, leading to cancer formation.

Where is the ALK gene located?

Cytogenetic Location: 2p23

Molecular Location on chromosome 2: base pairs 29,192,773 to 29,921,610

The ALK gene is located on the short (p) arm of chromosome 2 at position 23.

The ALK gene is located on the short (p) arm of chromosome 2 at position 23.

More precisely, the ALK gene is located from base pair 29,192,773 to base pair 29,921,610 on chromosome 2.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about ALK?

You and your healthcare professional may find the following resources about ALK helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the ALK gene or gene products?

  • ALK tyrosine kinase receptor
  • anaplastic lymphoma kinase
  • CD246
  • CD246 antigen
  • NBLST3

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding ALK?

acids ; amino acid ; arginine ; cancer ; cell ; cell proliferation ; chromosome ; constitutive ; differentiation ; DNA ; familial ; gene ; gene amplification ; glutamine ; inherited ; inversion ; kinase ; lymphoma ; marker ; mutation ; neuroblasts ; oxygen ; phosphate ; phosphorus ; phosphorylation ; proliferation ; protein ; rearrangement ; receptor ; signal transduction ; sporadic ; transduction ; translocation ; tumor ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ardini E, Magnaghi P, Orsini P, Galvani A, Menichincheri M. Anaplastic Lymphoma Kinase: role in specific tumours, and development of small molecule inhibitors for cancer therapy. Cancer Lett. 2010 Dec 28;299(2):81-94. doi: 10.1016/j.canlet.2010.09.001. Epub 2010 Oct 8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20934803?dopt=Abstract)
  • Janoueix-Lerosey I, Lequin D, Brugières L, Ribeiro A, de Pontual L, Combaret V, Raynal V, Puisieux A, Schleiermacher G, Pierron G, Valteau-Couanet D, Frebourg T, Michon J, Lyonnet S, Amiel J, Delattre O. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature. 2008 Oct 16;455(7215):967-70. doi: 10.1038/nature07398. (http://www.ncbi.nlm.nih.gov/pubmed/18923523?dopt=Abstract)
  • Mossé YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, Laureys G, Speleman F, Kim C, Hou C, Hakonarson H, Torkamani A, Schork NJ, Brodeur GM, Tonini GP, Rappaport E, Devoto M, Maris JM. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 2008 Oct 16;455(7215):930-5. doi: 10.1038/nature07261. Epub 2008 Aug 24. (http://www.ncbi.nlm.nih.gov/pubmed/18724359?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/238)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2011
Published: November 24, 2014