title: Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung.
abstract: Frequent losses of chromosome 19p have recently been observed in sporadic lung adenocarcinomas, targeting the location of a critical tumor suppressor gene. Here we performed fine mapping of the short arm of chromosome 19 and found that the LKB1/STK11 gene mapped in the minimal-deleted region. Because germ-line mutations at LKB1/STK11 result in the Peutz-Jeghers syndrome and an increased risk of cancer, we performed a detailed genetic screen of the LKB1/STK11 gene in lung tumors. We detected a high frequency of somatic alterations (mainly nonsense mutations) in primary lung adenocarcinomas and in lung cancer cell lines. Thus, our findings demonstrate for the first time that LKB1/STK11 inactivation is a very common event and may be integrally involved in the development of sporadic lung adenocarcinoma.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA. msanchez@cnio.es
authors.forename: Montserrat
authors.initials: M
authors.lastname: Sanchez-Cespedes
authors.forename: Paola
authors.initials: P
authors.lastname: Parrella
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.forename: James M
authors.initials: JM
authors.lastname: Engles
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics*; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases