title: A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers.
abstract: Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21 approximately p11.22 (62%), 12p12.1 approximately p13.1 (53%), 12p13.1 approximately p13.2 (53%), 11q14.1 approximately q14.2 (53%), 11p13 approximately p14.3 (47%), 9q21.13 approximately q21.32 (47%), and 4p15.1 approximately p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1 approximately q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs.
authors.affiliation: deCODE Genetics, Reykjavik, Iceland. jonthor@decode.is
authors.forename: Jon Thor
authors.initials: JT
authors.lastname: Bergthorsson
authors.forename: Bjarni Agnar
authors.initials: BA
authors.lastname: Agnarsson
authors.forename: Tomas
authors.initials: T
authors.lastname: Gudbjartsson
authors.forename: Kjartan
authors.initials: K
authors.lastname: Magnusson
authors.forename: Asgeir
authors.initials: A
authors.lastname: Thoroddsen
authors.forename: Birgir
authors.initials: B
authors.lastname: Palsson
authors.forename: Johannes
authors.initials: J
authors.lastname: Bjornsson
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gulcher
authors.forename: Gudmundur Vikar
authors.initials: GV
authors.lastname: Einarsson
authors.forename: Laufey Thora
authors.initials: LT
authors.lastname: Amundadottir
authors.forename: Rosa Bjork
authors.initials: RB
authors.lastname: Barkardottir
mesh_terms: D000293:Adolescent; D000328:Adult; D022981:Allelic Imbalance; D002675:Child, Preschool; D016162:Genes, Wilms Tumor; D016678:Genome; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein