Positional cloning identifies a novel cyclophilin as a candidate amplified oncogene in 1q21

Leonardo A. Meza-Zepeda, Anne Forus, Birgitte Lygren, Anine B. Dahlberg, Linda H. Godager, Andrew P. South, Ingo Marenholz, Maria Lioumi, Vivi Ann Flørenes, Gunhild M. Mælandsmo, Massimo Serra, Dietmar Mischke, Dean Nizetic, Jiannis Ragoussis, Maija Tarkkanen, Jahn M. Nesland, Sakari Knuutila, Ola Myklebost

Research output: Contribution to journalArticlepeer-review

Abstract

Gains of 1q21-q23 have been associated with metastasis and chemotherapy response, particularly in bladder cancer, hepatocellular carcinomas and sarcomas. By positional cloning of amplified genes by yeast artificial chromosome-mediated cDNA capture using magnetic beads, we have identified three candidate genes (COAS1, -2 and -3) in the amplified region in sarcomas. COAS1 and -2 showed higher amplification levels than COAS3. Most notably, amplification was very common in osteosarcomas, where in particular COAS2 was highly expressed. COAS1 has multiple repeats and shows no homology to previously described genes, whereas COAS2 is a novel member of the cyclosporin-binding peptidylprolyl isomerase family, very similar to cyclophilin A. COAS2 was overexpressed almost exclusively in aggressive metastatic or chemotherapy resistant tumours. Although COAS2 was generally more amplified than COAS1, it was not expressed in well-differentiated liposarcomas, where amplification of this region is very common. All three genes were found to be amplified and over-expressed also in breast carcinomas. The complex nature of the 1q21-23 amplicons and close proximity of the genes make unequivocal determination of the gene responsible difficult. Quite likely, the different genes may give selective advantages to different subsets of tumours.

Original languageEnglish
Pages (from-to)2261-2269
Number of pages9
JournalOncogene
Volume21
Issue number14
DOIs
Publication statusPublished - Mar 29 2002

Keywords

  • Amplification
  • Breast cancer
  • Chromosomel
  • Cyclophilin
  • Peptidyl-prolyl isomerase
  • Sarcoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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