Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma

Involvement of cyclin C in osteosarcoma

Norihide Ohata, Sachio Itou, Aki Yoshida, Toshiyuki Kunisada, Kunihiko Numoto, Yoshimi Jitsumori, Hirotaka Kanzaki, Toshihumi Ozaki, Kenji Shimizu, Mamoru Oouchida

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The molecular pathogenesis of osteosarcoma is very complicated and associated with chaotic abnormalities on many chromosomal arms. We analyzed 12 cases of osteosarcomas with comparative genomic hybridization (CGH) to identify chromosomal imbalances, and detected highly frequent chromosomal alterations in chromosome 6q, 8p, 10p and 10q. To define the narrow rearranged region on chromosome 6 with higher resolution, loss of heterozygosity (LOH) analysis was performed with 21 microsatellite markers. Out of 31 cases, 23 cases (74%) showed allelic loss at least with one marker on chromosome 6q. We identified two distinct commonly deleted regions on chromosome 6 using markers D6S1565 located at 6q16 and 6q23MS1 at 6q23. The expression analysis of genes located at the deleted region was performed, and the decreased mRNA expression of the CCNC gene, one of the regulators of cell cycle, was detected. Growth of osteosarcoma cell line was significantly suppressed after the CCNC cDNA transfection. Fine mapping of the deleted region containing a possible tumor suppressor gene and the transfection assay suggest that the CCNC is a candidate tumor suppressor gene.

Original languageEnglish
Pages (from-to)1153-1158
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume18
Issue number6
Publication statusPublished - Dec 2006

Fingerprint

Cyclin C
Loss of Heterozygosity
Osteosarcoma
Chromosomes, Human, Pair 6
Chromosomes
Tumor Suppressor Genes
Transfection
Gene Expression
Comparative Genomic Hybridization
Regulator Genes
Genetic Markers
Microsatellite Repeats
Cell Cycle
Complementary DNA
Cell Line
Messenger RNA
Growth

Keywords

  • Chromosomal aberration
  • Comparative genomic hybridization
  • cyclin C
  • Loss of heterozygosity
  • Osteosarcoma

ASJC Scopus subject areas

  • Genetics

Cite this

Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma : Involvement of cyclin C in osteosarcoma. / Ohata, Norihide; Itou, Sachio; Yoshida, Aki; Kunisada, Toshiyuki; Numoto, Kunihiko; Jitsumori, Yoshimi; Kanzaki, Hirotaka; Ozaki, Toshihumi; Shimizu, Kenji; Oouchida, Mamoru.

In: International Journal of Molecular Medicine, Vol. 18, No. 6, 12.2006, p. 1153-1158.

Research output: Contribution to journalArticle

Ohata, Norihide ; Itou, Sachio ; Yoshida, Aki ; Kunisada, Toshiyuki ; Numoto, Kunihiko ; Jitsumori, Yoshimi ; Kanzaki, Hirotaka ; Ozaki, Toshihumi ; Shimizu, Kenji ; Oouchida, Mamoru. / Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma : Involvement of cyclin C in osteosarcoma. In: International Journal of Molecular Medicine. 2006 ; Vol. 18, No. 6. pp. 1153-1158.
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AB - The molecular pathogenesis of osteosarcoma is very complicated and associated with chaotic abnormalities on many chromosomal arms. We analyzed 12 cases of osteosarcomas with comparative genomic hybridization (CGH) to identify chromosomal imbalances, and detected highly frequent chromosomal alterations in chromosome 6q, 8p, 10p and 10q. To define the narrow rearranged region on chromosome 6 with higher resolution, loss of heterozygosity (LOH) analysis was performed with 21 microsatellite markers. Out of 31 cases, 23 cases (74%) showed allelic loss at least with one marker on chromosome 6q. We identified two distinct commonly deleted regions on chromosome 6 using markers D6S1565 located at 6q16 and 6q23MS1 at 6q23. The expression analysis of genes located at the deleted region was performed, and the decreased mRNA expression of the CCNC gene, one of the regulators of cell cycle, was detected. Growth of osteosarcoma cell line was significantly suppressed after the CCNC cDNA transfection. Fine mapping of the deleted region containing a possible tumor suppressor gene and the transfection assay suggest that the CCNC is a candidate tumor suppressor gene.

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