EML4-ALK Fusion Lung Cancer: A Rare Acquired Event
A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently. Because the EML4-ALK fusion was only shown by a reverse transcription-polymerase...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-03-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608801261 |
| _version_ | 1828938132997799936 |
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| author | Sven Perner Patrick L Wagner Francesca Demichelis Rohit Mehra Christopher J LaFargue Benjamin J Moss Stefanie Arbogast Alex Soltermann Walter Weder Thomas J Giordano David G Beer David S Rickman Arul M Chinnaiyan Holger Moch Mark A Rubin |
| author_facet | Sven Perner Patrick L Wagner Francesca Demichelis Rohit Mehra Christopher J LaFargue Benjamin J Moss Stefanie Arbogast Alex Soltermann Walter Weder Thomas J Giordano David G Beer David S Rickman Arul M Chinnaiyan Holger Moch Mark A Rubin |
| author_sort | Sven Perner |
| collection | DOAJ |
| description | A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently. Because the EML4-ALK fusion was only shown by a reverse transcription-polymerase chain reaction approach, we developed fluorescent in situ hybridization assays to interrogate more than 600 NSCLCs using break-apart probes for EML4 and ALK. We found that EML4-ALK fusions occur in less than 3% of NSCLC samples and that EML4 and/or ALK amplifications also occur. We also observed that, in most cases in which an EML4/ALK alteration is detected, not all of the tumor cells harbor the lesion. By using a detailed multi-fluorescent in situ hybridization probe assay and reverse transcription-polymerase chain reaction, we have evidence that other, more common mechanisms besides gene inversion exist including the possibility of other fusion partners for ALK and EML4. Furthermore, we confirmed the NKX2-1 high-level amplification in a significant subset of NSCLC and found this amplification to be mutually exclusive to ALK and EML4 rearrangements. |
| first_indexed | 2024-12-14T02:36:51Z |
| format | Article |
| id | doaj.art-fa6a25e867ee4e21909b1c06f037b237 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-14T02:36:51Z |
| publishDate | 2008-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-fa6a25e867ee4e21909b1c06f037b2372022-12-21T23:20:06ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-03-0110329830210.1593/neo.07878EML4-ALK Fusion Lung Cancer: A Rare Acquired EventSven Perner0Patrick L Wagner1Francesca Demichelis2Rohit Mehra3Christopher J LaFargue4Benjamin J Moss5Stefanie Arbogast6Alex Soltermann7Walter Weder8Thomas J Giordano9David G Beer10David S Rickman11Arul M Chinnaiyan12Holger Moch13Mark A Rubin14Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USAMichigan Center for Translational Pathology, Department of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USAInstitute of Surgical Pathology, Department of Pathology, University Hospital of Zurich, Zurich, SwitzerlandInstitute of Surgical Pathology, Department of Pathology, University Hospital of Zurich, Zurich, SwitzerlandDivision of Thoracic Surgery, University Hospital of Zurich, Zurich, SwitzerlandDepartment of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USASection of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USAMichigan Center for Translational Pathology, Department of Pathology, Urology, Bioinformatics, and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USAInstitute of Surgical Pathology, Department of Pathology, University Hospital of Zurich, Zurich, SwitzerlandDepartment of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, USAA recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently. Because the EML4-ALK fusion was only shown by a reverse transcription-polymerase chain reaction approach, we developed fluorescent in situ hybridization assays to interrogate more than 600 NSCLCs using break-apart probes for EML4 and ALK. We found that EML4-ALK fusions occur in less than 3% of NSCLC samples and that EML4 and/or ALK amplifications also occur. We also observed that, in most cases in which an EML4/ALK alteration is detected, not all of the tumor cells harbor the lesion. By using a detailed multi-fluorescent in situ hybridization probe assay and reverse transcription-polymerase chain reaction, we have evidence that other, more common mechanisms besides gene inversion exist including the possibility of other fusion partners for ALK and EML4. Furthermore, we confirmed the NKX2-1 high-level amplification in a significant subset of NSCLC and found this amplification to be mutually exclusive to ALK and EML4 rearrangements.http://www.sciencedirect.com/science/article/pii/S1476558608801261 |
| spellingShingle | Sven Perner Patrick L Wagner Francesca Demichelis Rohit Mehra Christopher J LaFargue Benjamin J Moss Stefanie Arbogast Alex Soltermann Walter Weder Thomas J Giordano David G Beer David S Rickman Arul M Chinnaiyan Holger Moch Mark A Rubin EML4-ALK Fusion Lung Cancer: A Rare Acquired Event Neoplasia: An International Journal for Oncology Research |
| title | EML4-ALK Fusion Lung Cancer: A Rare Acquired Event |
| title_full | EML4-ALK Fusion Lung Cancer: A Rare Acquired Event |
| title_fullStr | EML4-ALK Fusion Lung Cancer: A Rare Acquired Event |
| title_full_unstemmed | EML4-ALK Fusion Lung Cancer: A Rare Acquired Event |
| title_short | EML4-ALK Fusion Lung Cancer: A Rare Acquired Event |
| title_sort | eml4 alk fusion lung cancer a rare acquired event |
| url | http://www.sciencedirect.com/science/article/pii/S1476558608801261 |
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