Anaplastic lymphoma kinase: Difference between revisions
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== Pathology == |
== Pathology == |
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The ALK gene can be oncogenic in |
The ALK gene can be oncogenic in three ways – by forming a fusion gene with any of several other genes, by gaining additional gene copies or with mutations of the actual DNA code for the gene itself. |
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=== Anaplastic large-cell lymphoma === |
=== Anaplastic large-cell lymphoma === |
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The EML4-ALK fusion gene is responsible for approximately 3-5% of [[non-small-cell lung cancer]](NSCLC). The vast majority of cases are adenocarcinomas. The standard test used to detect this gene in tumor samples is fluorescence in situ hybridization (FISH), but other techniques such as immunohistochemistry (IHC) and reverse-transcriptase PCR (RT-PCR) can also be used to detect lung cancers with an ALK gene fusion. ALK lung cancers are found in patients of all ages, although on average these patients may be somewhat younger. ALK lung cancers are more common in light cigarette smokers or nonsmokers, but a significant number of patients with this disease are current or former cigarette smokers. |
The EML4-ALK fusion gene is responsible for approximately 3-5% of [[non-small-cell lung cancer]](NSCLC). The vast majority of cases are adenocarcinomas. The standard test used to detect this gene in tumor samples is fluorescence in situ hybridization (FISH), but other techniques such as immunohistochemistry (IHC) and reverse-transcriptase PCR (RT-PCR) can also be used to detect lung cancers with an ALK gene fusion. ALK lung cancers are found in patients of all ages, although on average these patients may be somewhat younger. ALK lung cancers are more common in light cigarette smokers or nonsmokers, but a significant number of patients with this disease are current or former cigarette smokers. |
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=== Familial neuroblastoma === |
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| ⚫ | *Familial cases of [[neuroblastoma]]<ref name="pmid18724359">{{cite journal | author = 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 | title = Identification of ALK as a major familial neuroblastoma predisposition gene | journal = Nature | volume = 455 | issue = 7215 | pages = 930–5 | year = 2008 | month = October | pmid = 18724359 | pmc = 2672043 | doi = 10.1038/nature07261 | laysummary = http://www.prnewswire.com/cgi-bin/micro_stories.pl?ACCT=159681&TICK=CHOP&STORY=/www/story/08-25-2008/0004872713&EDATE=Aug+25,+2008 | laysource = PRNewswire-USNewswire }}</ref> |
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*[[Inflammatory myofibroblastic tumor]]<ref>{{cite journal|last=Lawrence|first=B|coauthors=Perez-Atayde, A; Hibbard, MK; Rubin, BP; Dal Cin, P; Pinkus, JL; Pinkus, GS; Xiao, S; Yi, ES; Fletcher, CD; Fletcher, JA|title=TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.|journal=The American journal of pathology|date=2000 Aug|volume=157|issue=2|pages=377-84|pmid=10934142}}</ref> |
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*Adult<ref>{{cite journal|last=Sukov|first=WR|coauthors=Hodge, JC; Lohse, CM; Akre, MK; Leibovich, BC; Thompson, RH; Cheville, JC|title=ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients.|journal=Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc|date=2012 Nov|volume=25|issue=11|pages=1516-25|pmid=22743654}}</ref><ref>{{cite journal|last=Sugawara|first=E|coauthors=Togashi, Y; Kuroda, N; Sakata, S; Hatano, S; Asaka, R; Yuasa, T; Yonese, J; Kitagawa, M; Mano, H; Ishikawa, Y; Takeuchi, K|title=Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method.|journal=Cancer|date=2012 Sep 15|volume=118|issue=18|pages=4427-36|pmid=22252991}}</ref> and pediatric<ref>{{cite journal|last=Debelenko|first=LV|coauthors=Raimondi, SC; Daw, N; Shivakumar, BR; Huang, D; Nelson, M; Bridge, JA|title=Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum.|journal=Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc|date=2011 Mar|volume=24|issue=3|pages=430-42|pmid=21076462}}</ref> <ref>{{cite journal|last=Mariño-Enríquez|first=A|coauthors=Ou, WB; Weldon, CB; Fletcher, JA; Pérez-Atayde, AR|title=ALK rearrangement in sickle cell trait-associated renal medullary carcinoma.|journal=Genes, chromosomes & cancer|date=2011 Mar|volume=50|issue=3|pages=146-53|pmid=21213368}}</ref> [[renal cell carcinoma]]s |
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*[[Esophageal cancer|Esophageal squamous cell carcinoma]]<ref>{{cite journal|last=Jazii|first=FR|coauthors=Najafi, Z; Malekzadeh, R; Conrads, TP; Ziaee, AA; Abnet, C; Yazdznbod, M; Karkhane, AA; Salekdeh, GH|title=Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer.|journal=World journal of gastroenterology : WJG|date=2006 Nov 28|volume=12|issue=44|pages=7104-12|pmid=17131471}}</ref><ref>{{cite journal|last=Yaakup|first=H|coauthors=Sagap, I; Fadilah, SA|title=Primary oesophageal Ki (CD30)-positive ALK+ anaplastic large cell lymphoma of T-cell phenotype.|journal=Singapore medical journal|date=2008 Oct|volume=49|issue=10|pages=e289-92|pmid=18946602}}</ref> |
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*[[Breast cancer]]<ref name="exon">{{cite journal|last=Lin|first=E|coauthors=Li, L; Guan, Y; Soriano, R; Rivers, CS; Mohan, S; Pandita, A; Tang, J; Modrusan, Z|title=Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers.|journal=Molecular cancer research : MCR|date=2009 Sep|volume=7|issue=9|pages=1466-76|pmid=19737969}}</ref> , notably the [[inflammatory breast cancer|inflammatory]] subtype<ref>{{cite journal|last=Tuma|first=RS|title=ALK gene amplified in most inflammatory breast cancers.|journal=Journal of the National Cancer Institute|date=2012 Jan 18|volume=104|issue=2|pages=87-8|pmid=22215853}}</ref> |
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*[[Anaplastic large cell lymphoma]] |
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*[[Colorectal cancer|Colonic adenocarcinoma]]<ref name=exon /> |
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*[[Inflammatory myofibroblastic tumor]] |
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*[[Anaplastic thyroid cancer]]<ref>{{cite journal|last=Murugan|first=AK|coauthors=Xing, M|title=Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene.|journal=Cancer research|date=2011 Jul 1|volume=71|issue=13|pages=4403-11|pmid=21596819}}</ref> |
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== ALK inhibitors == |
== ALK inhibitors == |
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Revision as of 11:53, 6 January 2013
Template:PBB Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ALK gene.[1][2]
Function
ALK plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system.[2]
The deduced amino acid sequences reveal that ALK is a novel receptor tyrosine kinase having a putative transmembrane domain and an extracellular domain. These sequences are absent in the product of the transforming NPM-ALK gene. ALK shows the greatest sequence similarity to LTK (leukocyte tyrosine kinase).
Pathology
The ALK gene can be oncogenic in three ways – by forming a fusion gene with any of several other genes, by gaining additional gene copies or with mutations of the actual DNA code for the gene itself.
Anaplastic large-cell lymphoma
The 2;5 chromosomal translocation is associated with approximately 60% anaplastic large-cell lymphomas (ALCLs). The translocation creates a fusion gene consisting of the ALK (anaplastic lymphoma kinase) gene and the nucleophosmin (NPM) gene: the 3' half of ALK, derived from chromosome 2 and coding for the catalytic domain, is fused to the 5' portion of NPM from chromosome 5. The product of the NPM-ALK fusion gene is oncogenic. In a smaller fraction of ALCL patients, the 3' half of ALK is fused to the 5' sequence of TPM3 gene, encoding for tropomyosin 3. In rare cases, ALK is fused to other 5' fusion partners, such as TFG, ATIC, CLTC1, TPM4, MSN, ALO17, MYH9.[3]
Non-small-cell lung cancer
The EML4-ALK fusion gene is responsible for approximately 3-5% of non-small-cell lung cancer(NSCLC). The vast majority of cases are adenocarcinomas. The standard test used to detect this gene in tumor samples is fluorescence in situ hybridization (FISH), but other techniques such as immunohistochemistry (IHC) and reverse-transcriptase PCR (RT-PCR) can also be used to detect lung cancers with an ALK gene fusion. ALK lung cancers are found in patients of all ages, although on average these patients may be somewhat younger. ALK lung cancers are more common in light cigarette smokers or nonsmokers, but a significant number of patients with this disease are current or former cigarette smokers.
Gene rearrangements in other tumours
- Familial cases of neuroblastoma[4]
- Inflammatory myofibroblastic tumor[5]
- Adult[6][7] and pediatric[8] [9] renal cell carcinomas
- Esophageal squamous cell carcinoma[10][11]
- Breast cancer[12] , notably the inflammatory subtype[13]
- Colonic adenocarcinoma[12]
- Anaplastic thyroid cancer[14]
ALK inhibitors
Xalkori (crizotinib), produced by Pfizer, was approved by the FDA for treatment of late stage lung cancer on August 26, 2011.[15] Early results of an initial Phase I trial with 82 patients with ALK induced lung cancer showed an overall response rate of 57%, a disease control rate at 8 weeks of 87% and progression free survival at 6 months of 72%.
See also
References
- ^ Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT (1994). "Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma". Science. 263 (5151): 1281–4. doi:10.1126/science.8122112. PMID 8122112.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b "Entrez Gene: ALK anaplastic lymphoma kinase (Ki-1)".
- ^ "Inhibitors of the anaplastic lymphoma kinase". Expert Opin. Investig. Drugs. 21 (7): 985–994. 2012. doi:10.1517/13543784.2012.690031. PMID 22612599.
{{cite journal}}:|first=missing|last=(help) - ^ 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 (2008). "Identification of ALK as a major familial neuroblastoma predisposition gene". Nature. 455 (7215): 930–5. doi:10.1038/nature07261. PMC 2672043. PMID 18724359.
{{cite journal}}: Unknown parameter|laysource=ignored (help); Unknown parameter|laysummary=ignored (help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Lawrence, B (2000 Aug). "TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors". The American journal of pathology. 157 (2): 377–84. PMID 10934142.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Sukov, WR (2012 Nov). "ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients". Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 25 (11): 1516–25. PMID 22743654.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Sugawara, E (2012 Sep 15). "Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method". Cancer. 118 (18): 4427–36. PMID 22252991.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Debelenko, LV (2011 Mar). "Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum". Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 24 (3): 430–42. PMID 21076462.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Mariño-Enríquez, A (2011 Mar). "ALK rearrangement in sickle cell trait-associated renal medullary carcinoma". Genes, chromosomes & cancer. 50 (3): 146–53. PMID 21213368.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Jazii, FR (2006 Nov 28). "Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer". World journal of gastroenterology : WJG. 12 (44): 7104–12. PMID 17131471.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Yaakup, H (2008 Oct). "Primary oesophageal Ki (CD30)-positive ALK+ anaplastic large cell lymphoma of T-cell phenotype". Singapore medical journal. 49 (10): e289-92. PMID 18946602.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ a b Lin, E (2009 Sep). "Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers". Molecular cancer research : MCR. 7 (9): 1466–76. PMID 19737969.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Tuma, RS (2012 Jan 18). "ALK gene amplified in most inflammatory breast cancers". Journal of the National Cancer Institute. 104 (2): 87–8. PMID 22215853.
{{cite journal}}: Check date values in:|date=(help) - ^ Murugan, AK (2011 Jul 1). "Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene". Cancer research. 71 (13): 4403–11. PMID 21596819.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ "Xalkori Approved for Lung Cancer". FDA.
Further reading
External links
- ALK+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ALK Correlations, Experiments, Publications and Clinical Trials
- GeneReviews/NCBI/NIH/UW entry on ALK-Related Neuroblastoma Susceptibility
- OMIM entries on ALK-Related Neuroblastoma Susceptibility
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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