Abstract
Introduction
Oncogenic fusion of anaplastic lymphoma kinase (ALK) with echinoderm microtubule associated
protein like 4 protein or other partner genes occurs in 3% to 6% of lung adenocarcinomas.
Although fluorescence in situ hybridization (FISH) is the accepted standard for detecting
anaplastic lymphoma receptor tyrosine kinase gene (ALK) gene rearrangement that gives rise to new fusion genes, not all ALK FISH–positive patients respond to ALK inhibitor therapies. We report here an ALK FISH–positive patient-derived xenograft (PDX) that was nonresponsive to crizotinib
therapy.
Methods
The PDX patient human lung cancer (PHLC402) was established in NOD/SCID mice from
a patient with resected pT4N1M0 lung adenocarcinoma. ALK gene status was investigated using the standard FISH break-apart assay, reverse-transcriptase
quantitative polymerase chain reaction, RNA sequencing and immunohistochemical assay
using the 5A4 antibody. PHLC402 was treated with crizotinib (50 mg/kg) by daily oral
gavage.
Results
ALK FISH assay was positive in both the primary patient tumor and PDX, which were negative
for ALK protein expression by immunohistochemical analysis. ALK fusion product was
not detected by RNA sequencing and reverse-transcriptase quantitative polymerase chain
reaction comparing the 5′ and 3′ ALK transcript levels. Crizotinib treatment of PHLC402
grown in mice resulted in no tumor response.
Conclusion
ALK protein expression may be necessary for ALK FISH–positive lung cancer to be responsive to ALK inhibitor therapy.
Keywords
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Article info
Publication history
Published online: September 06, 2016
Accepted:
August 22,
2016
Received in revised form:
August 20,
2016
Received:
July 5,
2016
Footnotes
Disclosure: The authors declare no conflict of interest.
Identification
Copyright
© 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
