Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: involvement of cyclin C in osteosarcoma.
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.
Ohata
Norihide
N
Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
Ito
Sachio
S
Yoshida
Aki
A
Kunisada
Toshiyuki
T
Numoto
Kunihiko
K
Jitsumori
Yoshimi
Y
Kanzaki
Hirotaka
H
Ozaki
Toshifumi
T
Shimizu
Kenji
K
Ouchida
Mamoru
M
D045744:Cell Line, Tumor; D002896:Chromosomes, Human, Pair 6; D056745:Cyclin C; D016213:Cyclins / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D009693:Nucleic Acid Hybridization; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000378:metabolism
C503674:CCNC protein, human; D056745:Cyclin C; D016213:Cyclins; D018076:DNA, Complementary; D005819:Genetic Markers; D012333:RNA, Messenger