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KRAS oncogene substitutions in Korean NSCLC patients: Clinical implication and relationship with pAKT and RalGTPases expression

Authors
 Eun Young Kim  ;  Arum Kim  ;  Se Kyu Kim  ;  Hyung Jung Kim  ;  Joon Chang  ;  Chul Min Ahn  ;  Jae Seok Lee  ;  Hyo Sup Shim  ;  Yoon Soo Chang 
Citation
 Lung Cancer, Vol.85(2) : 299-305, 2014 
Journal Title
 Lung Cancer 
ISSN
 0169-5002 
Issue Date
2014
Abstract
OBJECTIVES: Since different conformation of each KRAS mutant leads to inherent downstream signaling, its distribution, influence on the clinical outcome, and effect on the signaling mediators were investigated in the Korean NSCLC patients whose tumor have KRAS mutation. MATERIALS AND METHODS: Mutation at KRAS codons 12 and 13 was evaluated in 1420 Korean NSCLC by direct sequencing and expression of RalA, RalB, and pAKT-Ser473 was evaluated by immunohistochemistry in 30 cases whose KRAS mutant tumor tissues were available. RESULTS: Eighty-two (5.8%) out of 1420 patients harbored a KRAS mutation either in codon 12 or 13. Gly12Asp was the most frequent (34.1%), followed by Gly12Cys (22.0%) and Gly12Val (13.4%). Transversion at codons 12 and 13, which includes Gly12Cys, Gly12Val, Gly12Ala, Gly13Cys, and Gly12Phe was detected in 45 cases (54.9%) and transition, including Gly12Asp, Gly12Ser, and Gly13Asp was detected in 37 cases (45.1%). Male and smoking history were associated with transversion (p=0.001 and 0.006, respectively; χ(2)-test), and multivariate analysis showed that gender was an independent influencing factor (p=0.026; Cochran-Mantel-Haenszel test). Multivariate analysis on survival revealed that KRAS mutation subtype did not influence overall survival of the patients with KRAS mutations after adjustment for age, gender, performance status, and stage. There were no differences in the nuclear and cytoplasmic expression of pAKT-Ser473 between transversion and transition mutants. Expression of Ral-GTPases, RalA and RalB, did not differ between transversion and transition mutants, however, strong expression of RalB in the tissue of patients with KRAS mutants was associated with advanced stages (P-value=0.020, χ(2)-test). CONCLUSIONS: In this study population, not only the frequency of KRAS mutation but also the distribution of its subtypes differed from those of Western studies, with unique influencing factors. Clinical outcome and expression of pAKT-Ser473, RalA, and RalB did not differ among subtypes.
Full Text
http://www.sciencedirect.com/science/article/pii/S0169500214001834
DOI
10.1016/j.lungcan.2014.04.012
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Medical Education (의학교육학과) > 1. Journal Papers
Yonsei Authors
김세규(Kim, Se Kyu)
김아름(Kim, A Rum)
김은영(Kim, Eun Young) ORCID logo https://orcid.org/0000-0002-3281-5744
김형중(Kim, Hyung Jung) ORCID logo https://orcid.org/0000-0003-2498-0683
심효섭(Shim, Hyo Sup) ORCID logo https://orcid.org/0000-0002-5718-3624
안철민(Ahn, Chul Min)
이재석(Lee, Jae Seok)
장윤수(Chang, Yoon Soo) ORCID logo https://orcid.org/0000-0003-3340-4223
장준(Chang, Joon) ORCID logo https://orcid.org/0000-0003-4542-6841
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99116
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