Ladder-like amplification of the type I interferon gene cluster in the human osteosarcoma cell line MG63

• Published in: Chromosome research Vol. 16; no. 8; pp. 1177 - 1192
• Main Authors: Marella, Narasimharao V, Zeitz, Michael J, Malyavantham, Kishore S, Pliss, Artem, Matsui, Sei-ichi, Goetze, Sandra, Bode, Juergen, Raska, Ivan, Berezney, Ronald
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : Springer Netherlands 01.12.2008; Springer Netherlands; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; array comparative genomic hybridization (aCGH); Biomedical and Life Sciences; Cancer; Cell Biology; Cell Line, Tumor; Chromosomal Proteins, Non-Histone - genetics; Chromosome Painting; Chromosomes; Chromosomes, Human, Pair 9 - genetics; Comparative Genomic Hybridization; Fluorescence in situ hybridization; fluorescence in-situ hybridization (FISH); gene amplification; Genomics; Human Genetics; human osteosarcoma cells; Humans; IFN chromosome; In Situ Hybridization, Fluorescence; Interferon; interferon (IFN) gene cluster; Interferon Type I - genetics; Karyotyping; Life Sciences; Multigene Family - genetics; Nucleic Acid Amplification Techniques - methods; Plant Genetics and Genomics; spectral karayotyping (SKY); interferon (IFN) gene cluster; human osteosarcoma cells; array comparative genomic hybridization (aCGH); fluorescence in-situ hybridization (FISH); spectral karayotyping (SKY); gene amplification; IFN chromosome
• ISSN: 0967-3849; 1573-6849; 1573-6849
• DOI: 10.1007/s10577-008-1267-x

The organization of the type I interferon (IFN) gene cluster (9p21.3) was studied in a human osteosarcoma cell line (MG63). Array comparative genomic hybridization (aCGH) showed an amplification of ~6-fold which ended at both ends of the gene cluster with a deletion that extended throughout the 9p21.3 band. Spectral karyotyping (SKY) combined with fluorescence in-situ hybridization (FISH) identified an arrangement of the gene cluster in a ladder-like array of 5-7 'bands' spanning a single chromosome termed the 'IFN chromosome'. Chromosome painting revealed that the IFN chromosome is derived from components of chromosomes 4, 8 and 9. Labelling with centromeric probes demonstrated a ladder-like amplification of centromeric 4 and 9 sequences that co-localized with each other and a similar banding pattern of chromosome 4, as well as alternating with the IFN gene clusters. In contrast, centromere 8 was not detected on the IFN chromosome. One of the amplified centromeric 9 bands was identified as the functional centromere based on its location at the chromosome constriction and immunolocalization of the CENP-C protein. A model is presented for the generation of the IFN chromosome that involves breakage-fusion-bridge events.