title: Genetic and epigenetic alterations of the LKB1 gene and their associations with mutations in TP53 and EGFR pathway genes in Korean non-small cell lung cancers.
abstract: BACKGROUND
  Liver kinase 1 (LKB1) plays a critical barrier role in lung tumorigenesis by controlling initiation, differentiation and metastasis. We searched for genetic and epigenetic alterations of the LKB1 gene in Korean non-small cell lung cancers (NSCLCs) and correlated the results with clinicopathological features. We also investigated the relationship between genetic and epigenetic alterations of LKB1 and mutations in the TP53 gene and epidermal growth factor receptor (EGFR) pathway genes.
  
  
  METHODS
  A total of 159 NSCLCs were analyzed for loss of heterozygosity (LOH) at microsatellite loci D19S886, and D19S878. Mutations and methylation status of LKB1 were examined by direct sequencing and a methylation-specific polymerase chain reaction, respectively.
  
  
  RESULTS
  A somatic mutation was found in one of the 159 tumors. LOH and promoter methylation was detected in 19.5% (31/159) and 13.2% (21/159) of the tumors, respectively. Four of the 159 tumors had concomitant LOH and methylation of LKB1. In total, 30.2% of the 159 NSCLCs harbored LKB1 LOH or promoter methylation, which were correlated with down-regulation of gene expression. LKB1 LOH was more frequent in males, smokers, and tumors with a TP53 mutation than in females, never-smokers, and tumors without a TP53 mutation, respectively. However, no significant correlation between LKB1 alterations and mutations in EGFR pathway genes was found.
  
  
  CONCLUSIONS
  These results suggest that the prevalence of LKB1 genetic and epigenetic alterations in NSCLCs vary depending on patient ethnicity. Our results show that LKB1 alterations often occur simultaneously with mutations in EGFR pathway genes.
authors.affiliation: Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Su Man
authors.initials: SM
authors.lastname: Lee
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Na
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Lee
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Yi Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Ghil Suk
authors.initials: GS
authors.lastname: Yoon
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D056910:Republic of Korea; D015398:Signal Transduction
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
keywords: Inactivation; LKB1; Non-small cell lung cancer