title: Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients.
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.
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Koivunen
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: A M
authors.initials: AM
authors.lastname: Rogers
authors.forename: J O
authors.initials: JO
authors.lastname: Park
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: K
authors.initials: K
authors.lastname: Naoki
authors.forename: I
authors.initials: I
authors.lastname: Okamoto
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: B Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: M
authors.initials: M
authors.lastname: Meyerson
authors.forename: K-K
authors.initials: KK
authors.lastname: Wong
authors.forename: W G
authors.initials: WG
authors.lastname: Richards
authors.forename: D J
authors.initials: DJ
authors.lastname: Sugarbaker
authors.forename: B E
authors.initials: BE
authors.lastname: Johnson
authors.forename: P A
authors.initials: PA
authors.lastname: Jänne
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D044466:Asian People / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D066246:ErbB Receptors; C482119:BRAF protein, human; D017346:Protein Serine-Threonine Kinases; D048493:Proto-Oncogene Proteins B-raf; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases