Universität zu Köln

Li, Tianhong, Maus, Martin K. H., Desai, Sonal J., Beckett, Laurel A., Stephens, Craig, Huang, Eric, Hsiang, Jack, Zeger, Gary, Danenberg, Kathleen D., Astrow, Stephanie H. and Gandara, David R. (2014). Large-Scale Screening and Molecular Characterization of EML4-ALK Fusion Variants in Archival Non-Small-Cell Lung Cancer Tumor Specimens Using Quantitative Reverse Transcription Polymerase Chain Reaction Assays. J. Thorac. Oncol., 9 (1). S. 18 - 26. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1556-1380

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Abstract

Introduction: The objective of this study was to identify and characterize echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase fusion (EML4-ALK+) cancers by variant-specific, quantitative reverse transcription polymerase chain reaction (RT-PCR) assays in a large cohort of North American non-small-cell lung cancer (NSCLC) patients. Methods: We developed a panel of single and multiplex RT-PCR assays suitable for rapid and accurate detection of the eight most common EML4-ALK+ variants and ALK gene expression in archival formalin-fixed, paraffin-embedded NSCLC specimens. EGFR and KRAS genotyping and thymidylate synthase RNA level by RT-PCR assays were available in a subset of patients. Results: Between December 2009 and September 2012, 7344 NSCLC specimens were tested. An EML4-ALK+ transcript was detected in 200 cases (2.7%), including 109 V1 (54.5%), 20 V2 (10.0%), 68 V3 (34.0%), and three V5a (1.5%) variants. Median age was 54.5 years (range, 23-89), and 104 patients (52.0%) were women. The great majority (n=188, 94.0%) of EML4-ALK+ NSCLC tumors had adenocarcinoma histology. ALK expression level varied significantly among different EML4-ALK+ variants and individual tumors. Only one case each of concurrent EGFR or KRAS mutation was detected. The median thymidylate synthase RNA level from 85 EML4-ALK+ cancers was significantly lower compared with that of EML4-ALK-negative lung adenocarcinomas (2.02 versus 3.29, respectively, p<0.001). Conclusions: This panel of variant-specific, quantitative RT-PCR assays detects common EML4-ALK+ variants as well as ALK gene expression level in archival formalin-fixed paraffin-embedded NSCLC specimens. These RT-PCR assays may be useful as an adjunct to the standard fluorescence in situ hybridization assay to better understand biologic variability and response patterns to anaplastic lymphoma kinase inhibitors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Li, Tianhong UNSPECIFIED UNSPECIFIED UNSPECIFIED Maus, Martin K. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Desai, Sonal J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beckett, Laurel A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stephens, Craig UNSPECIFIED UNSPECIFIED UNSPECIFIED Huang, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED Hsiang, Jack UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeger, Gary UNSPECIFIED UNSPECIFIED UNSPECIFIED Danenberg, Kathleen D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Astrow, Stephanie H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gandara, David R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-450325
DOI:	10.1097/JTO.0000000000000030
Journal or Publication Title:	J. Thorac. Oncol.
Volume:	9
Number:	1
Page Range:	S. 18 - 26
Date:	2014
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1556-1380
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANAPLASTIC LYMPHOMA KINASE; EGFR MUTATION; ALK; GENE; INHIBITOR; IDENTIFICATION; REARRANGEMENTS; PCR; CHEMOTHERAPY; CRIZOTINIB Multiple languages Oncology; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/45032