What are the genetic changes related to neuroblastoma ? 
 Neuroblastoma and other cancers occur when a buildup of genetic mutations in critical genesthose that control cell growth and division (proliferation) or maturation (differentiation)allow 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. When neuroblastoma is associated with somatic mutations, it is called sporadic neuroblastoma. It is thought that somatic mutations in at least two genes are required to cause sporadic neuroblastoma. Less commonly, gene mutations that increase the risk of developing cancer can be inherited from a parent. When the mutation associated with neuroblastoma is inherited, the condition is called familial neuroblastoma. Mutations in the ALK and PHOX2B genes have been shown to increase the risk of developing sporadic and familial neuroblastoma. It is likely that there are other genes involved in the formation of neuroblastoma.  Several mutations in the ALK gene are involved in the development of sporadic and familial neuroblastoma. The ALK gene provides instructions for making a protein called anaplastic lymphoma kinase. Although the specific function of this protein is unknown, it appears to play an important role in cell proliferation. Mutations in the ALK gene result in an abnormal version of anaplastic lymphoma kinase that is constantly turned on (constitutively activated). Constitutively active anaplastic lymphoma kinase may induce abnormal proliferation of immature nerve cells and lead to neuroblastoma.  Several mutations in the PHOX2B gene have been identified in sporadic and familial neuroblastoma. The PHOX2B gene is important for the formation and differentiation of nerve cells. Mutations in this gene are believed to interfere with the PHOX2B protein's role in promoting nerve cell differentiation. This disruption of differentiation results in an excess of immature nerve cells and leads to neuroblastoma.  Deletion of certain regions of chromosome 1 and chromosome 11 are associated with neuroblastoma. Researchers believe the deleted regions in these chromosomes could contain a gene that keeps cells from growing and dividing too quickly or in an uncontrolled way, called a tumor suppressor gene. When a tumor suppressor gene is deleted, cancer can occur. The KIF1B gene is a tumor suppressor gene located in the deleted region of chromosome 1, and mutations in this gene have been identified in some people with familial neuroblastoma, indicating it is involved in neuroblastoma development or progression. There are several other possible tumor suppressor genes in the deleted region of chromosome 1. No tumor suppressor genes have been identified in the deleted region of chromosome 11.  Another genetic change found in neuroblastoma is associated with the severity of the disease but not thought to cause it. About 25 percent of people with neuroblastoma have extra copies of the MYCN gene, a phenomenon called gene amplification. It is unknown how amplification of this gene contributes to the aggressive nature of neuroblastoma.