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

• Published in: Molecular cytogenetics Vol. 5; no. 1; p. 44
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London BioMed Central 03.12.2012; BMC
• Subjects: Adenocarcinoma; ALK amplification; ALK protein; ALK rearrangement; Biomedical and Life Sciences; Biomedicine; Crizotinib; Cytogenetics; EGFR; Epidermal growth factor receptors; FISH; Fluorescence in situ hybridization; Fluorescent indicators; Formaldehyde; gene rearrangement; Human Genetics; K-Ras protein; KRAS; Lung carcinoma; Lymphoma; Molecular Medicine; Mutation; Non-small cell lung cancer; Non-small cell lung carcinoma; Polymerase chain reaction; Protein-tyrosine kinase; Protein-tyrosine kinase receptors; Adenocarcinoma; Crizotinib; FISH; amplification; rearrangement; Non-small cell lung cancer
• ISSN: 1755-8166; 1755-8166
• DOI: 10.1186/1755-8166-5-44

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.