title: Detection of ALK rearrangements in lung cancer patients using a homebrew PCR assay.
abstract: Lung cancer patients with anaplastic lymphoma kinase (ALK) rearrangements are candidates for targeted therapeutics. However, patients must be tested with a companion diagnostic assay to realize their ALK rearrangement status. We analyzed the publicly available E-GEOD-31210 microarray dataset and identified a non-coding RNA, sweyjawbu, which is strongly associated with ALK rearrangements. We validated these results using quantitative real-time PCR in an independent cohort consisting of 4 cell lines and 83 clinical samples. We could differentiate between ALK rearrangement-positive and -negative lung cancer samples by comparing sweyjawbu expression. Additionally, ALK rearrangement status was determined by comparing the expression of the 5' and 3' regions of the ALK transcript or by detecting known ALK hybrid subtypes. Thus, using our homebrew PCR assay, we were able to accurately detect ALK rearrangements, which could be used for diagnostic screening of lung cancer patients. The prototype could potentially be transferred to an automatic multiplex PCR platform (FilmArray) to differentiate between ALK rearrangement-positive and -negative patients in point-of-care settings.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: JianHua
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: YongMing
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Tissue bank, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: ZhuanXu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jiabing
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhai
authors.affiliation: Fudan University Shanghai Cancer Center-Institut Mérieux Lab, Fudan University Shanghai Cancer Center, Shanghai, China.|Medical Device Development Department (MD3), bioMérieux Co, Ltd, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jialei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Fudan University Shanghai Cancer Center-Institut Mérieux Lab, Fudan University Shanghai Cancer Center, Shanghai, China.|Medical Device Development Department (MD3), bioMérieux Co, Ltd, Shanghai, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Ye
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D055088:Early Detection of Cancer / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D062085:RNA, Long Noncoding / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: anaplastic lymphoma kinase (ALK); lung carcinomas; quantitative real-time PCR; rearrangement; sweyjawbu