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Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas
BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with ALK rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576271/ https://www.ncbi.nlm.nih.gov/pubmed/23198868 http://dx.doi.org/10.1186/1755-8166-5-44 |
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author | Dai, Zunyan Kelly, JoAnn C Meloni-Ehrig, Aurelia Slovak, Marilyn L Boles, Debra Christacos, Nicole C Bryke, Christine R Schonberg, Steven A Otani-Rosa, Jennifer Pan, Qiulu Ho, Albert K Sanders, Heather R Zhang, Zhong J Jones, Dan Mowrey, Philip N |
author_facet | Dai, Zunyan Kelly, JoAnn C Meloni-Ehrig, Aurelia Slovak, Marilyn L Boles, Debra Christacos, Nicole C Bryke, Christine R Schonberg, Steven A Otani-Rosa, Jennifer Pan, Qiulu Ho, Albert K Sanders, Heather R Zhang, Zhong J Jones, Dan Mowrey, Philip N |
author_sort | Dai, Zunyan |
collection | PubMed |
description | BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with ALK rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK. RESULTS: In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the ALK gene was performed on formalin fixed paraffin-embedded tissue to determine the incidence of ALK rearrangements and hybridization patterns in a large unselected cohort of 1387 patients with a referred diagnosis of non-small cell lung cancer (1011 of these patients had a histologic diagnosis of adenocarcinoma). The abnormal FISH signal patterns varied from a single split signal to complex patterns. Among 49 abnormal samples (49/1387, 3.5%), 32 had 1 to 3 split signals. Fifteen samples had deletions of the green 5(′) end of the ALK signal, and 1 of these 15 samples showed amplification of the orange 3(′) end of the ALK signal. Two patients showed a deletion of the 3(′)ALK signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with ALK rearrangements detected by FISH were confirmed to have EML4-ALK fusions by multiplex RT-PCR. Among the 45 ALK-rearranged samples tested, only 1 EGFR mutation (T790M) was detected. Two KRAS mutations were detected among 24 ALK-rearranged samples tested. CONCLUSIONS: In a large unselected series, the frequency of ALK gene rearrangement detected by FISH was approximately 3.5% of lung carcinoma, and 3.7% of patients with lung adenocarcinoma, with variant signal patterns frequently detected. Rare cases with coexisting KRAS and EGFR mutations were seen. |
format | Online Article Text |
id | pubmed-3576271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35762712013-02-20 Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas Dai, Zunyan Kelly, JoAnn C Meloni-Ehrig, Aurelia Slovak, Marilyn L Boles, Debra Christacos, Nicole C Bryke, Christine R Schonberg, Steven A Otani-Rosa, Jennifer Pan, Qiulu Ho, Albert K Sanders, Heather R Zhang, Zhong J Jones, Dan Mowrey, Philip N Mol Cytogenet Research BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with ALK rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK. RESULTS: In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the ALK gene was performed on formalin fixed paraffin-embedded tissue to determine the incidence of ALK rearrangements and hybridization patterns in a large unselected cohort of 1387 patients with a referred diagnosis of non-small cell lung cancer (1011 of these patients had a histologic diagnosis of adenocarcinoma). The abnormal FISH signal patterns varied from a single split signal to complex patterns. Among 49 abnormal samples (49/1387, 3.5%), 32 had 1 to 3 split signals. Fifteen samples had deletions of the green 5(′) end of the ALK signal, and 1 of these 15 samples showed amplification of the orange 3(′) end of the ALK signal. Two patients showed a deletion of the 3(′)ALK signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with ALK rearrangements detected by FISH were confirmed to have EML4-ALK fusions by multiplex RT-PCR. Among the 45 ALK-rearranged samples tested, only 1 EGFR mutation (T790M) was detected. Two KRAS mutations were detected among 24 ALK-rearranged samples tested. CONCLUSIONS: In a large unselected series, the frequency of ALK gene rearrangement detected by FISH was approximately 3.5% of lung carcinoma, and 3.7% of patients with lung adenocarcinoma, with variant signal patterns frequently detected. Rare cases with coexisting KRAS and EGFR mutations were seen. BioMed Central 2012-12-03 /pmc/articles/PMC3576271/ /pubmed/23198868 http://dx.doi.org/10.1186/1755-8166-5-44 Text en Copyright ©2012 Dai et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Dai, Zunyan Kelly, JoAnn C Meloni-Ehrig, Aurelia Slovak, Marilyn L Boles, Debra Christacos, Nicole C Bryke, Christine R Schonberg, Steven A Otani-Rosa, Jennifer Pan, Qiulu Ho, Albert K Sanders, Heather R Zhang, Zhong J Jones, Dan Mowrey, Philip N Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas |
title | Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas |
title_full | Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas |
title_fullStr | Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas |
title_full_unstemmed | Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas |
title_short | Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas |
title_sort | incidence and patterns of alk fish abnormalities seen in a large unselected series of lung carcinomas |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576271/ https://www.ncbi.nlm.nih.gov/pubmed/23198868 http://dx.doi.org/10.1186/1755-8166-5-44 |
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