Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas
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- 作者：Zunyan Dai (1)
JoAnn C Kelly (1)
Aurelia Meloni-Ehrig (2)
Marilyn L Slovak (1)
Debra Boles (1)
Nicole C Christacos (1)
Christine R Bryke (1)
Steven A Schonberg (1)
Jennifer Otani-Rosa (1)
Qiulu Pan (3)
Albert K Ho (3) (4)
Heather R Sanders (5)
Zhong J Zhang (5)
Dan Jones (3) (4)
Philip N Mowrey (1) - 关键词：ALK rearrangement ; ALK amplification ; FISH ; KRAS ; EGFR ; Non ; small cell lung cancer ; Adenocarcinoma ; Crizotinib
- 刊名：Molecular Cytogenetics
- 出版年：2012
- 出版时间：December 2012
- 年：2012
- 卷：5
- 期：1
- 全文大小：532KB
- 参考文献：1. Siegel R, Naishadham D, Jemal A:
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10. Katayama R, Shaw AT, Khan TM, Mino-Kenudson M, Solomon BJ, Halmos B, Jessop NA, Wain JC, Yeo AT, Benes C, / et al.: - 作者单位：Zunyan Dai (1)
JoAnn C Kelly (1)
Aurelia Meloni-Ehrig (2)
Marilyn L Slovak (1)
Debra Boles (1)
Nicole C Christacos (1)
Christine R Bryke (1)
Steven A Schonberg (1)
Jennifer Otani-Rosa (1)
Qiulu Pan (3)
Albert K Ho (3) (4)
Heather R Sanders (5)
Zhong J Zhang (5)
Dan Jones (3) (4)
Philip N Mowrey (1)
1. Department of Cytogenetics, Quest Diagnostics Nichols Institute, 14225 Newbrook Drive, Chantilly, VA, 20151, USA
2. Department of Cytogenetics, AmeriPath, 8150 Chancellor Dr. Suite 110, Orlando, FL, 32809, USA
3. Department of Molecular Oncology, Quest Diagnostics Nichols Institute, 14225 Newbrook Drive, Chantilly, VA, 20151, USA
4. Department of Pathology, Quest Diagnostics Nichols Institute, 14225 Newbrook Drive, Chantilly, VA, 20151, USA
5. Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA - ISSN：1755-8166
文摘
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-/sup> end of the ALK signal, and 1 of these 15 samples showed amplification of the orange 3-/sup> end of the ALK signal. Two patients showed a deletion of the 3-/sup> 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.