Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients

Br J Cancer. 2008 Jul 22;99(2):245-52. doi: 10.1038/sj.bjc.6604469. Epub 2008 Jul 1.

Abstract

Somatic mutations of LKB1 tumour suppressor gene have been detected in human cancers including non-small cell lung cancer (NSCLC). The relationship between LKB1 mutations and clinicopathological characteristics and other common oncogene mutations in NSCLC is inadequately described. In this study we evaluated tumour specimens from 310 patients with NSCLC including those with adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma histologies. Tumours were obtained from patients of US (n=143) and Korean (n=167) origin and screened for LKB1, KRAS, BRAF, and EGFR mutations using RT-PCR-based SURVEYOR-WAVE method followed by Sanger sequencing. We detected mutations in the LKB1 gene in 34 tumours (11%). LKB1 mutation frequency was higher in NSCLC tumours of US origin (17%) compared with 5% in NSCLCs of Korean origin (P=0.001). They tended to occur more commonly in adenocarcinomas (13%) than in squamous cell carcinomas (5%) (P=0.066). LKB1 mutations associated with smoking history (P=0.007) and KRAS mutations (P=0.042) were almost mutually exclusive with EGFR mutations (P=0.002). The outcome of stages I and II NSCLC patients treated with surgery alone did not significantly differ based on LKB1 mutation status. Our study provides clinical and molecular characteristics of NSCLC, which harbour LKB1 mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / ethnology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • ErbB Receptors / genetics
  • European Continental Ancestry Group / genetics*
  • Genes, Tumor Suppressor*
  • Genes, ras
  • Genetic Predisposition to Disease
  • Humans
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mutation*
  • Protein-Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins B-raf / genetics

Substances

  • STK11 protein, human
  • ErbB Receptors
  • BRAF protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins B-raf