title: Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer.
abstract: Inactivation of p53, which represents the most prevalent genetic alteration in lung cancer, has been shown to play a crucial role in the acquisition of genomic instability. We examined 44 lung cancer specimens to search for mutations in the CHK1 and CHK2 genes, which have been suggested to play roles in regulating p53 after DNA damage. We found that the CHK2 gene was somatically mutated in lung cancer in vivo, although at a low frequency, and that a previously undescribed shorter isoform of CHK1 was expressed preferentially in small cell lung cancer in a tumor-predominant manner. Additional studies are warranted to investigate the functional significance of these changes as well as the potential involvement of other components in this important pathway to maintain genomic stability.
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Haruki
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Tatematsu
authors.forename: H
authors.initials: H
authors.lastname: Konishi
authors.forename: T
authors.initials: T
authors.lastname: Harano
authors.forename: A
authors.initials: A
authors.lastname: Masuda
authors.forename: H
authors.initials: H
authors.lastname: Osada
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000595:Amino Acid Sequence; D015139:Blotting, Southern; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004252:DNA Mutational Analysis; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D020033:Protein Isoforms; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020033:Protein Isoforms; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases