The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.

Hdl Handle:
http://hdl.handle.net/10147/207908
Title:
The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.
Authors:
Kelleher, Fergal C; McDermott, Ray
Affiliation:
Department of Medical Oncology, Adelaide and Meath Hospital, Dublin, Ireland., fergalkelleher@hotmail.com
Citation:
Eur J Cancer. 2010 Sep;46(13):2357-68. Epub 2010 May 5.
Journal:
European journal of cancer (Oxford, England : 1990)
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207908
DOI:
10.1016/j.ejca.2010.04.006
PubMed ID:
20451371
Abstract:
The anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin's lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3/4 (TMP3/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic possibilities.
Language:
eng
MeSH:
Antineoplastic Agents/therapeutic use; Carcinoma, Non-Small-Cell Lung/genetics/therapy; *Chromosome Aberrations; Chromosomes, Human, Pair 2/*genetics; Drug Synergism; Gene Amplification; Humans; Lung Neoplasms/genetics/therapy; Lymphoma, Large-Cell, Anaplastic/genetics/therapy; Mutation/genetics; Neoplasms/*genetics/therapy; Neuroblastoma/genetics/therapy; Protein-Tyrosine Kinases/antagonists & inhibitors/*genetics; Pyrimidines/therapeutic use; Pyrroles/therapeutic use; Receptor Protein-Tyrosine Kinases; Receptor, IGF Type 1/antagonists & inhibitors
ISSN:
1879-0852 (Electronic); 0959-8049 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorKelleher, Fergal Cen_GB
dc.contributor.authorMcDermott, Rayen_GB
dc.date.accessioned2012-02-01T10:49:46Z-
dc.date.available2012-02-01T10:49:46Z-
dc.date.issued2012-02-01T10:49:46Z-
dc.identifier.citationEur J Cancer. 2010 Sep;46(13):2357-68. Epub 2010 May 5.en_GB
dc.identifier.issn1879-0852 (Electronic)en_GB
dc.identifier.issn0959-8049 (Linking)en_GB
dc.identifier.pmid20451371en_GB
dc.identifier.doi10.1016/j.ejca.2010.04.006en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207908-
dc.description.abstractThe anaplastic lymphoma kinase gene (ALK) is a gene on chromosome 2p23 that has expression restricted to the brain, testis and small intestine but is not expressed in normal lymphoid tissue. It has similarity to the insulin receptor subfamily of kinases and is emerging as having increased pathologic and potential therapeutic importance in malignant disease. This gene was originally established as being implicated in the pathogenesis of rare diseases including inflammatory myofibroblastic tumour (IMT) and ALK-positive anaplastic large cell lymphoma, which is a subtype of non-Hodgkin's lymphoma. Recently the number of diseases in which ALK is implicated in their pathogenesis has increased. In 2007, an inversion of chromosome 2 involving ALK and a fusion partner gene in a subset of non-small cell lung cancer was discovered. In 2008, publications emerged implicating ALK in familial and sporadic cases of neuroblastoma, a childhood cancer of the sympatho-adrenal system. Chromosomal abnormalities involving ALK are translocations, amplifications or mutations. Chromosomal translocations are the longest recognised ALK genetic abnormality. When translocations occur a fusion gene is created between ALK and a gene partner. This has been described in ALK-positive anaplastic large cell lymphoma in which ALK is fused to NPM (nucleolar protein gene) and in non-small cell lung cancer where ALK is fused to EML4 (Echinoderm microtubule-associated protein 4). The most frequently described partner genes in inflammatory myofibroblastic tumour are tropomyosin 3/4 (TMP3/4), however in IMTs a diversity of ALK fusion partners have been found, with the ability to homodimerise a common characteristic. Point mutations and amplification of the ALK gene occur in the childhood cancer neuroblastoma. Therapeutic targeting of ALK fusion genes using tyrosine kinase inhibition, vaccination using an ALK specific antigen and treatment using viral vectors for RNAi are emerging potential therapeutic possibilities.en_GB
dc.language.isoengen_GB
dc.subject.meshAntineoplastic Agents/therapeutic useen_GB
dc.subject.meshCarcinoma, Non-Small-Cell Lung/genetics/therapyen_GB
dc.subject.mesh*Chromosome Aberrationsen_GB
dc.subject.meshChromosomes, Human, Pair 2/*geneticsen_GB
dc.subject.meshDrug Synergismen_GB
dc.subject.meshGene Amplificationen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLung Neoplasms/genetics/therapyen_GB
dc.subject.meshLymphoma, Large-Cell, Anaplastic/genetics/therapyen_GB
dc.subject.meshMutation/geneticsen_GB
dc.subject.meshNeoplasms/*genetics/therapyen_GB
dc.subject.meshNeuroblastoma/genetics/therapyen_GB
dc.subject.meshProtein-Tyrosine Kinases/antagonists & inhibitors/*geneticsen_GB
dc.subject.meshPyrimidines/therapeutic useen_GB
dc.subject.meshPyrroles/therapeutic useen_GB
dc.subject.meshReceptor Protein-Tyrosine Kinasesen_GB
dc.subject.meshReceptor, IGF Type 1/antagonists & inhibitorsen_GB
dc.titleThe emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.en_GB
dc.contributor.departmentDepartment of Medical Oncology, Adelaide and Meath Hospital, Dublin, Ireland., fergalkelleher@hotmail.comen_GB
dc.identifier.journalEuropean journal of cancer (Oxford, England : 1990)en_GB
dc.description.provinceLeinster-

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