Incidence and patterns of <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomas
<p>Abstract</p> <p>Background</p> <p>Anaplastic lymphoma receptor tyrosine kinase (<it>ALK</it>) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with <it>ALK</it> rearrangements do not...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-12-01
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| Series: | Molecular Cytogenetics |
| Subjects: | |
| Online Access: | http://www.molecularcytogenetics.org/content/5/1/44 |
| _version_ | 1811266068326383616 |
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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 | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Anaplastic lymphoma receptor tyrosine kinase (<it>ALK</it>) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with <it>ALK</it> rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK.</p> <p>Results</p> <p>In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the <it>ALK</it> gene was performed on formalin fixed paraffin-embedded tissue to determine the incidence of <it>ALK</it> 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<sup>′</sup> end of the <it>ALK</it> signal, and 1 of these 15 samples showed amplification of the orange 3<sup>′</sup> end of the <it>ALK</it> signal. Two patients showed a deletion of the 3<sup>′</sup><it>ALK</it> signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with <it>ALK</it> rearrangements detected by FISH were confirmed to have <it>EML4-ALK</it> fusions by multiplex RT-PCR. Among the 45 <it>ALK</it>-rearranged samples tested, only 1 <it>EGFR</it> mutation (T790M) was detected. Two <it>KRAS</it> mutations were detected among 24 <it>ALK</it>-rearranged samples tested.</p> <p>Conclusions</p> <p>In a large unselected series, the frequency of <it>ALK</it> 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 <it>KRAS</it> and <it>EGFR</it> mutations were seen.</p> |
| first_indexed | 2024-04-12T20:35:25Z |
| format | Article |
| id | doaj.art-db6545a5ae324a1bb0b12d7fb49f0968 |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-04-12T20:35:25Z |
| publishDate | 2012-12-01 |
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| series | Molecular Cytogenetics |
| spelling | doaj.art-db6545a5ae324a1bb0b12d7fb49f09682022-12-22T03:17:36ZengBMCMolecular Cytogenetics1755-81662012-12-01514410.1186/1755-8166-5-44Incidence and patterns of <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomasDai ZunyanKelly JoAnn CMeloni-Ehrig AureliaSlovak Marilyn LBoles DebraChristacos Nicole CBryke Christine RSchonberg Steven AOtani-Rosa JenniferPan QiuluHo Albert KSanders Heather RZhang Zhong JJones DanMowrey Philip N<p>Abstract</p> <p>Background</p> <p>Anaplastic lymphoma receptor tyrosine kinase (<it>ALK</it>) gene rearrangements have been reported in 2-13% of patients with non-small cell lung cancer (NSCLC). Patients with <it>ALK</it> rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors (TKIs); however, they do benefit from small molecule inhibitors targeting ALK.</p> <p>Results</p> <p>In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the <it>ALK</it> gene was performed on formalin fixed paraffin-embedded tissue to determine the incidence of <it>ALK</it> 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<sup>′</sup> end of the <it>ALK</it> signal, and 1 of these 15 samples showed amplification of the orange 3<sup>′</sup> end of the <it>ALK</it> signal. Two patients showed a deletion of the 3<sup>′</sup><it>ALK</it> signal. Thirty eight of these 49 samples (38/1011, 3.7%) were among the 1011 patients with confirmed adenocarcinoma. Five of 8 patients with <it>ALK</it> rearrangements detected by FISH were confirmed to have <it>EML4-ALK</it> fusions by multiplex RT-PCR. Among the 45 <it>ALK</it>-rearranged samples tested, only 1 <it>EGFR</it> mutation (T790M) was detected. Two <it>KRAS</it> mutations were detected among 24 <it>ALK</it>-rearranged samples tested.</p> <p>Conclusions</p> <p>In a large unselected series, the frequency of <it>ALK</it> 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 <it>KRAS</it> and <it>EGFR</it> mutations were seen.</p>http://www.molecularcytogenetics.org/content/5/1/44<it>ALK</it> rearrangement<it>ALK</it> amplificationFISH<it>KRAS</it><it>EGFR</it>Non-small cell lung cancerAdenocarcinomaCrizotinib |
| spellingShingle | 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 <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomas Molecular Cytogenetics <it>ALK</it> rearrangement <it>ALK</it> amplification FISH <it>KRAS</it> <it>EGFR</it> Non-small cell lung cancer Adenocarcinoma Crizotinib |
| title | Incidence and patterns of <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomas |
| title_full | Incidence and patterns of <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomas |
| title_fullStr | Incidence and patterns of <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomas |
| title_full_unstemmed | Incidence and patterns of <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomas |
| title_short | Incidence and patterns of <it>ALK</it> FISH abnormalities seen in a large unselected series of lung carcinomas |
| title_sort | incidence and patterns of it alk it fish abnormalities seen in a large unselected series of lung carcinomas |
| topic | <it>ALK</it> rearrangement <it>ALK</it> amplification FISH <it>KRAS</it> <it>EGFR</it> Non-small cell lung cancer Adenocarcinoma Crizotinib |
| url | http://www.molecularcytogenetics.org/content/5/1/44 |
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