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The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma

 H. R. Kim  ;  S. M. Lim  ;  H. J. Kim  ;  S. K. Hwang  ;  J. K. Park  ;  E. Shin  ;  M. K. Bae  ;  S.-H. I. Ou  ;  J. Wang  ;  S. S. Jewell  ;  D. R. Kang  ;  R. A. Soo  ;  H. Haack  ;  J. H. Kim  ;  H. S. Shim  ;  B. C. Cho 
 ANNALS OF ONCOLOGY, Vol.24(9) : 2364-2370, 2013 
Journal Title
Issue Date
Adenocarcinoma/drug therapy ; Adenocarcinoma/genetics* ; Adult ; Aged ; Antigens, Differentiation, B-Lymphocyte/genetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cell Line, Tumor ; Cell Survival/drug effects ; Disease-Free Survival ; Female ; Gene Frequency/genetics ; Gene Rearrangement/genetics ; Glutamates/pharmacology ; Glutamates/therapeutic use ; Guanine/analogs & derivatives ; Guanine/pharmacology ; Guanine/therapeutic use ; Histocompatibility Antigens Class II/genetics ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics* ; Male ; Middle Aged ; Mutation/genetics ; Pemetrexed ; Protein-Tyrosine Kinases/genetics* ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins/genetics* ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins p21(ras) ; Pyrazoles/pharmacology ; Pyridines/pharmacology ; Pyrimidines/pharmacology ; Quinazolines/pharmacology ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptor, Epidermal Growth Factor/genetics ; Recombinant Fusion Proteins/genetics* ; Recombinant Fusion Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Smoking ; Treatment Outcome ; ras Proteins/genetics
ROS1 ; lung adenocarcinoma ; never smoker ; outcome
BACKGROUND: To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma.

PATIENTS AND METHODS: We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization.

RESULTS: Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01).

CONCLUSIONS: The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Hang(김주항)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Bae, Mi Kyung(배미경)
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
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