Dataset Information

Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas.

ABSTRACT:

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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.

SUBMITTER: Dai Z

PROVIDER: S-EPMC3576271 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas.

Dai Zunyan Z Kelly Joann C JC Meloni-Ehrig Aurelia A Slovak Marilyn L ML Boles Debra D Christacos Nicole C NC Bryke Christine R CR Schonberg Steven A SA Otani-Rosa Jennifer J Pan Qiulu Q Ho Albert K AK Sanders Heather R HR Zhang Zhong J ZJ Jones Dan D Mowrey Philip N PN

Molecular cytogenetics 20121203 1

<h4>Unlabelled</h4><h4>Background</h4>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.<h4>Results</h4>In this study, fluorescence in situ hybridization (FISH) using a break-apart probe for the ALK gene was performed on formali ...[more]

PMID: 23198868

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Dataset Information

Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas.

Unlabelled

Background

Results

Conclusions

Publications

Incidence and patterns of ALK FISH abnormalities seen in a large unselected series of lung carcinomas.

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