The Analysis of Cytogenetics of Giant Cell Tumors
M Kanamori, T Yasuda, K Suzuki, T Hori, T Kimura. University of Toyama, Toyama City, Toyama, Japan
Background: Multiple studies have identified the prevalence and clinical significance of a various genetic markers including telomeric association in giant cell tumors (GCTs). It is very important to analyze the DNA copy number change, to identify the molecular events in GCTs.
Design: In this study, we have used array-based comparative genomic hybridization (CGH) for high resolution mapping of copy number changes in 8 giant cell tumors.
Results: Primary bone tumors showed copy number gains in 12.2% of the genome and losses in 11.2%. Genetic instability, showing aberrations in more than 100 in 287 clones, were identified in 4 patients. Six clones showed high-level amplification in these 4 cases with genetic instability. They were MYC (8q24), CREBBP (16p13.3), BRCA1 (17q21), THRA (17q11.2), D19S238E (19qtel), TNFRSF6B (DCR3; 20q13). Ten clones of NRAS (1p13.2), D2S447 (2qtel), D3S1274;ROBO1 (3p12-13), D4S114 (4p16.3), PIMI (6p21.2), MOS (8q11), HRAS (11p15.5), GLI (12q13.2-13), AKT1 (14q32), D17S1670 (17q23) were commonly low in genetic instability cases. In telomeric area analyzed 73 clones, loss of D2S447 (2qtel), and gain of WI-6509 (11qtel) and D19S238E (19qtel) were observed. Our results of gain of MYC (8q24) gene was supported the findings of c-myc gene over-expression.
Conclusions: Gambri, et al has already reported c-myc mRNA was over-expressed in 38% of GCT. The loss of NRAS was observed in 6 cases (75%) out of 8 GCTs. NRAS mutations have detected prostate cancers before. However, there was no report the relashionship GCTs and NRAS before. Our present array-based CGH analysis indicated to 16 genes showing genetic instability, as the target gene on oncogenesis of GCTs.
Category: Bone & Soft Tissue
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 22, Tuesday Morning