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J Thorac Oncol
2011 Jan 01;61:21-7. doi: 10.1097/JTO.0b013e3181fb7cd6.
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Increased ALK gene copy number and amplification are frequent in non-small cell lung cancer.
Salido M
,
Pijuan L
,
Martínez-Avilés L
,
Galván AB
,
Cañadas I
,
Rovira A
,
Zanui M
,
Martínez A
,
Longarón R
,
Sole F
,
Serrano S
,
Bellosillo B
,
Wynes MW
,
Albanell J
,
Hirsch FR
,
Arriola E
.
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INTRODUCTION: Translocation of the anaplastic lymphoma kinase (ALK) gene is involved in the tumorigenesis of a subset of non-small cell lung carcinomas (NSCLCs) and identifies patients sensitive to ALK inhibitors. ALK copy number changes and amplification, which plays an oncogenic role in tumors such as neuroblastoma, are poorly characterized in NSCLC. We aimed to study the prevalence of ALK copy number changes and their correlation to ALK protein expression, epidermal growth factor receptor (EGFR) status, and clinicopathological data in patients with NSCLC.
METHODS: ALK status was evaluated by fluorescence in situ hybridization (FISH). Specimens with ALK translocation were studied for echinoderm microtubule-associated protein-like 4 (EML4), KIF5B, and TFG status. ALK expression was assessed by immunohistochemistry. EGFR gene and protein status were evaluated in adenocarcinomas. Survival analysis was performed.
RESULTS: One hundred seven NSCLC cases were evaluated. There were two cases of EML4-ALK translocation and one with an atypical translocation of ALK. Both cases of EML4-ALK translocation had ALK protein expression, whereas in the rest, ALK was undetected. Eleven cases (10%) exhibited ALK amplification and 68 (63%) copy number gains. There was an association between ALK amplification and EGFR FISH positivity (p < 0.0001) but not with prognosis. In conclusion, EML4-ALK translocation is a rare event in NSCLC.
CONCLUSION: The study reveals a significant frequency of ALK amplification and its association with EGFR FISH positivity in lung adenocarcinomas. Based on these findings, a potential role of ALK amplification in the response to ALK inhibitors alone or combined with EGFR inhibitors in NSCLC merits further studies.
Cappuzzo,
Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer.
2005, Pubmed
Cappuzzo,
Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer.
2005,
Pubmed
Cappuzzo,
Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients.
2005,
Pubmed
Carén,
High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours.
2008,
Pubmed
Chen,
Oncogenic mutations of ALK kinase in neuroblastoma.
2008,
Pubmed
Chung,
Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry.
2005,
Pubmed
Gascoyne,
ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases.
2003,
Pubmed
George,
Activating mutations in ALK provide a therapeutic target in neuroblastoma.
2008,
Pubmed
Griffin,
Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.
1999,
Pubmed
Hirsch,
Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis.
2003,
Pubmed
Inamura,
EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset.
2009,
Pubmed
,
Echinobase
Inamura,
EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers.
2008,
Pubmed
,
Echinobase
Janoueix-Lerosey,
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.
2008,
Pubmed
Jemal,
Cancer statistics, 2008.
2008,
Pubmed
Ma,
Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive anaplastic lymphoma kinase (ALK) tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis.
2000,
Pubmed
Martelli,
EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues.
2009,
Pubmed
,
Echinobase
Mino-Kenudson,
A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry.
2010,
Pubmed
Mok,
Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
2009,
Pubmed
Morris,
Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
1994,
Pubmed
Mossé,
Identification of ALK as a major familial neuroblastoma predisposition gene.
2008,
Pubmed
NULL,
NCI-Navy Medical Oncology Branch cell line supplement.
1996,
Pubmed
Paez,
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
2004,
Pubmed
Perner,
EML4-ALK fusion lung cancer: a rare acquired event.
2008,
Pubmed
Rikova,
Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.
2007,
Pubmed
Rodig,
Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population.
2009,
Pubmed
Salido,
Polysomy of chromosome 17 in breast cancer tumors showing an overexpression of ERBB2: a study of 175 cases using fluorescence in situ hybridization and immunohistochemistry.
2005,
Pubmed
Settleman,
Cell culture modeling of genotype-directed sensitivity to selective kinase inhibitors: targeting the anaplastic lymphoma kinase (ALK).
2009,
Pubmed
Shaw,
Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK.
2009,
Pubmed
Soda,
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
2007,
Pubmed
,
Echinobase
Takeuchi,
KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer.
2009,
Pubmed
Turke,
Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC.
2010,
Pubmed
Uramoto,
Which biomarker predicts benefit from EGFR-TKI treatment for patients with lung cancer?
2007,
Pubmed