title: Gain of a region on 7p22.3, containing MAD1L1, is the most frequent event in small-cell lung cancer cell lines.
abstract: Small-cell lung cancer (SCLC) is a highly aggressive lung neoplasm, which accounts for 20% of yearly lung cancer cases. The lack of knowledge of the progenitor cell type for SCLC precludes the definition of a normal gene expression profile and has hampered the identification of gene expression changes, while the low resolution of conventional genomic screens such as comparative genomic hybridization (CGH) and loss of heterozygosity analysis limit our ability to fine-map genetic alterations. The recent advent of whole genome tiling path array CGH enables profiling of segmental DNA copy number gains and losses at a resolution 100 times that of conventional methods. Here we report the analysis of 14 SCLC cell lines and six matched normal B-lymphocyte lines. We detected 7p22.3 copy number gain in 13 of the 14 SCLC lines and 0 of the 6 matched normal lines. In 4 of the 14 cell lines, this gain is present as a 350 kbp gene specific copy number gain centered at MAD1L1 (the human homologue of the yeast gene MAD1). Fluorescence in situ hybridization validated the array CGH finding. Intriguingly, MAD1L1 has been implicated to have tumor-suppressing functions. Our data suggest a more complex role for this gene, as MAD1L1 is the most frequent copy number gain in SCLC cell lines.
authors.affiliation: British Columbia Cancer Research Centre, Vancouver, BC, Canada. bcoe@bccrc.ca
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Coe
authors.forename: Eric H L
authors.initials: EH
authors.lastname: Lee
authors.forename: Bryan
authors.initials: B
authors.lastname: Chi
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: Stephen
authors.initials: S
authors.lastname: Lam
authors.forename: Calum
authors.initials: C
authors.lastname: MacAulay
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology; D018288:Carcinoma, Small Cell / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; D009687:Nuclear Proteins