title: Mapping of homozygous deletions in verified esophageal adenocarcinoma cell lines and xenografts.
abstract: Human esophageal adenocarcinoma (EAC) cell lines and xenografts are powerful tools in the search for genetic alterations because these models are composed of pure human cancer cell populations without admixture of normal human cells. In particular detection of homozygous deletions (HDs) is easier using these pure populations of cancer cells. Identification of HDs could potentially lead to the subsequent identification of new tumor suppressor genes (TSGs) involved in esophageal adenocarcinogenesis. Genome wide single nucleotide polymorphism (SNP) arrays were used to identify HDs in 10 verified EAC cell lines and nine EAC xenografts. In total, 61 HDs (range 1-6 per sample) were detected and confirmed by polymerase chain reaction. Besides HDs observed in common fragile genomic regions (n = 26), and gene deserts (n = 8), 27 HDs were located in gene-containing regions. HDs were noted for known TSGs, including CDKN2A, SMAD4 and CDH3/CDH1. Twenty-two new chromosomal regions were detected harboring potentially new TSGs involved in EAC carcinogenesis. Two of these regions of homozygous loss, encompassing the ITGAV and RUNX1 gene, were detected in multiple samples indicating a potential role in the carcinogenesis of EAC. To exclude culturing artifacts, these last two deletions were confirmed by fluorescent in situ hybridization in the primary tumors of which the involved cell lines and xenografts were derived. In summary, in this report we describe the identification of HDs in a series of verified EAC cell lines and xenografts. The deletions documented here are a step forward identifying the key genes involved in EAC development.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. j.boonstra1@antoniusziekenhuis.nl
authors.forename: Jurjen J
authors.initials: JJ
authors.lastname: Boonstra
authors.forename: Ronald
authors.initials: R
authors.lastname: van Marion
authors.forename: Hannie J C W
authors.initials: HJ
authors.lastname: Douben
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Timms
authors.forename: Victor
authors.initials: V
authors.lastname: Abkevich
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: Annelies
authors.initials: A
authors.lastname: de Klein
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D056915:DNA Copy Number Variations; D004938:Esophageal Neoplasms / Q000235:genetics*; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006720:Homozygote; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D014183:Transplantation, Heterologous / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D039564:Integrin alphaV; C493728:RUNX1 protein, human; D025521:Tumor Suppressor Proteins