PMID- 24418728
OWN - NLM
STAT- MEDLINE
DCOM- 20141028
LR  - 20220331
IS  - 1943-7811 (Electronic)
IS  - 1525-1578 (Linking)
VI  - 16
IP  - 2
DP  - 2014 Mar
TI  - A single-tube multiplexed assay for detecting ALK, ROS1, and RET fusions in lung 
      cancer.
PG  - 229-43
LID - S1525-1578(13)00261-4 [pii]
LID - 10.1016/j.jmoldx.2013.11.007 [doi]
AB  - Approximately 7% of non-small cell lung carcinomas (NSCLCs) harbor oncogenic 
      fusions involving ALK, ROS1, and RET. Although tumors harboring ALK fusions are 
      highly sensitive to crizotinib, emerging preclinical and clinical data 
      demonstrate that patients with ROS1 or RET fusions may also benefit from 
      inhibitors targeting these kinases. Using a transcript-based method, we designed 
      a combination of 3' overexpression and fusion-specific detection strategies to 
      detect ALK, ROS1 and RET fusion transcripts in NSCLC tumors. We validated the 
      assay in 295 NSCLC specimens and showed that the assay is highly sensitive and 
      specific. ALK results were 100% concordant with fluorescence in situ 
      hybridization (FISH) (n = 52) and 97.8% concordant with IHC (n = 179) 
      [sensitivity, 96.8% (95% CI 91.0%-98.9%); specificity, 98.8% (95% CI 
      93.6%-99.8%)]. For ROS1 and RET, we also observed 100% concordance with FISH (n = 
      46 and n = 15, respectively). We identified seven ROS1 and 14 RET fusion-positive 
      tumors and confirmed the fusion status by RT-PCR and FISH. One RET fusion 
      involved a novel partner, cutlike homeobox 1 gene (CUX1), yielding an in-frame 
      CUX1-RET fusion. ROS1 and RET fusions were significantly enriched in tumors 
      without KRAS/EGFR/ALK alterations. ALK/ROS1/RET/EGFR/KRAS alterations were 
      mutually exclusive. As a single-tube assay, this test shows promise as a more 
      practical and cost-effective screening modality for detecting rare but targetable 
      fusions in NSCLC.
CI  - Copyright (c) 2014 American Society for Investigative Pathology and the Association 
      for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
FAU - Lira, Maruja E
AU  - Lira ME
AD  - Oncology Research Unit, Pfizer Inc, San Diego, California.
FAU - Choi, Yoon-La
AU  - Choi YL
AD  - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine, Seoul, Republic of Korea.
FAU - Lim, Sun Min
AU  - Lim SM
AD  - Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College 
      of Medicine, Seoul, Republic of Korea.
FAU - Deng, Shibing
AU  - Deng S
AD  - Oncology Research Unit, Pfizer Inc, San Diego, California.
FAU - Huang, Donghui
AU  - Huang D
AD  - Oncology Research Unit, Pfizer Inc, San Diego, California.
FAU - Ozeck, Mark
AU  - Ozeck M
AD  - Oncology Research Unit, Pfizer Inc, San Diego, California.
FAU - Han, Joungho
AU  - Han J
AD  - Department of Medical Oncology, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine, Seoul, Republic of Korea.
FAU - Jeong, Ji Yun
AU  - Jeong JY
AD  - Department of Pathology, Kyungpook National University Hospital, Daegu, Republic 
      of Korea.
FAU - Shim, Hyo Sup
AU  - Shim HS
AD  - Department of Pathology, Kyungpook National University Hospital, Daegu, Republic 
      of Korea.
FAU - Cho, Byoung Chul
AU  - Cho BC
AD  - Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College 
      of Medicine, Seoul, Republic of Korea.
FAU - Kim, Jhingook
AU  - Kim J
AD  - Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine, Seoul, Republic of Korea. Electronic address: 
      jkimsmc@skku.edu.
FAU - Ahn, Myung-Ju
AU  - Ahn MJ
AD  - Department of Medical Oncology, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine, Seoul, Republic of Korea. Electronic address: 
      silkahn@skku.edu.
FAU - Mao, Mao
AU  - Mao M
AD  - Oncology Research Unit, Pfizer Inc, San Diego, California. Electronic address: 
      mao_m@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140110
PL  - United States
TA  - J Mol Diagn
JT  - The Journal of molecular diagnostics : JMD
JID - 100893612
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (ROS1 protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Non-Small-Cell Lung/diagnosis/genetics
MH  - Female
MH  - Gene Order
MH  - Genetic Testing/*methods
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*diagnosis/*genetics
MH  - Male
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Protein-Tyrosine Kinases/*genetics
MH  - Proto-Oncogene Proteins/*genetics
MH  - Proto-Oncogene Proteins c-ret/*genetics
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Reproducibility of Results
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sensitivity and Specificity
MH  - Sequence Analysis, DNA
MH  - Transcription, Genetic
MH  - Translocation, Genetic
EDAT- 2014/01/15 06:00
MHDA- 2014/10/29 06:00
CRDT- 2014/01/15 06:00
PHST- 2013/01/29 00:00 [received]
PHST- 2013/10/06 00:00 [revised]
PHST- 2013/11/06 00:00 [accepted]
PHST- 2014/01/15 06:00 [entrez]
PHST- 2014/01/15 06:00 [pubmed]
PHST- 2014/10/29 06:00 [medline]
AID - S1525-1578(13)00261-4 [pii]
AID - 10.1016/j.jmoldx.2013.11.007 [doi]
PST - ppublish
SO  - J Mol Diagn. 2014 Mar;16(2):229-43. doi: 10.1016/j.jmoldx.2013.11.007. Epub 2014 
      Jan 10.