TY - JOUR
T1 - RASSF1A promoter methylation and Kras2 mutations in non small cell lung cancer
AU - Li, Jie
AU - Zhang, Zhongqiu
AU - Dait, Zunyan
AU - Popkie, Anthony P.
AU - Plass, Christoph
AU - Morrison, Carl
AU - Wang, Yian
AU - You, Ming
N1 - Funding Information:
Abbreviations: LOH, loss of heterozygosity; NSCLC, non small cell lung cancer; PCR, polymerase chain reaction; MSP, methylation-specific PCR Address all correspondence to: Ming You, MD, PhD, Department of Surgery, The Washington University School of Medicine, Campus Box 8109, 660 South Euclid Avenue, St. Louis, MO 63110, USA. E-mail: [email protected] 1This work was supported by Public Health Service grants R01CA58554 (M.Y.), R01CA78797 (Y.W.), and R41CA093204 (M.Y.). Received 11 April 2003; Accepted 1 May 2003.
PY - 2003
Y1 - 2003
N2 - In the present studies, we investigated the correlation between RASSF1A promoter methylation status and Kras2 mutations in 65 primary non small cell lung cancer (NSCLC) including 33 adenocarcinomas, 12 large cell carcinomas, and 20 squamous cell carcinomas. Mutational analysis of Kras2 showed: 30% (10 of 33) of adenocarcinomas, 25% (3 of 12) of large cell carcinomas, and only 5% (1 of 20) of squamous cell carcinomas contained activated Kras2 mutation at codon 12 or 13. RASSF1A promoter region CpG island methylation was detected in adenocarcinomas (55%), large cell carcinomas (25%), and squamous cell carcinomas (25%). Interestingly, combined RASSF1A methylation and Kras2 mutation data show that only ∼7% adenocarcinomas/large cell carcinomas exhibited both KRASSF1A promoter methylation and Kras2 mutation, whereas 24% adenocarcinomas, 50% large cell carcinomas, and 70% squamous cell carcinomas showed neither Kras2 mutation nor RASSF1A promoter methylation. These results showed that the majority of the primary NSCLCs with Kras2 mutations lack RASSF1A inactivation, and both RASSF1A inactivation and Kras2 mutation events occur frequently in adenocarcinomas and large cell carcinomas. Our results indicate a trend of inverse relationship between Kras2 activation and RASSF1A promoter methylation in the majority of human lung adenocarcinomas and large cell carcinomas.
AB - In the present studies, we investigated the correlation between RASSF1A promoter methylation status and Kras2 mutations in 65 primary non small cell lung cancer (NSCLC) including 33 adenocarcinomas, 12 large cell carcinomas, and 20 squamous cell carcinomas. Mutational analysis of Kras2 showed: 30% (10 of 33) of adenocarcinomas, 25% (3 of 12) of large cell carcinomas, and only 5% (1 of 20) of squamous cell carcinomas contained activated Kras2 mutation at codon 12 or 13. RASSF1A promoter region CpG island methylation was detected in adenocarcinomas (55%), large cell carcinomas (25%), and squamous cell carcinomas (25%). Interestingly, combined RASSF1A methylation and Kras2 mutation data show that only ∼7% adenocarcinomas/large cell carcinomas exhibited both KRASSF1A promoter methylation and Kras2 mutation, whereas 24% adenocarcinomas, 50% large cell carcinomas, and 70% squamous cell carcinomas showed neither Kras2 mutation nor RASSF1A promoter methylation. These results showed that the majority of the primary NSCLCs with Kras2 mutations lack RASSF1A inactivation, and both RASSF1A inactivation and Kras2 mutation events occur frequently in adenocarcinomas and large cell carcinomas. Our results indicate a trend of inverse relationship between Kras2 activation and RASSF1A promoter methylation in the majority of human lung adenocarcinomas and large cell carcinomas.
KW - Kras2
KW - Lung cancer
KW - Methylation
KW - Mutations
KW - RASSF1A
UR - http://www.scopus.com/inward/record.url?scp=0042856354&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042856354&partnerID=8YFLogxK
U2 - 10.1016/s1476-5586(03)80029-5
DO - 10.1016/s1476-5586(03)80029-5
M3 - Article
C2 - 14511407
AN - SCOPUS:0042856354
SN - 1522-8002
VL - 5
SP - 362
EP - 366
JO - Neoplasia
JF - Neoplasia
IS - 4
ER -