Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma Journal Article
| Authors: | Man, T. K.; Lu, X. Y.; Jaeweon, K.; Perlaky, L.; Harris, C. P.; Shah, S.; Ladanyi, M.; Gorlick, R.; Lau, C. C.; Rao, P. H. |
| Article Title: | Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma |
| Abstract: | Background: Osteosarcoma is a highly malignant bone neoplasm of children and young adults. It is characterized by extremely complex karyotypes and high frequency of chromosomal amplifications. Currently, only the histological response (degree of necrosis) to therapy represent gold standard for predicting the outcome in a patient with non-metastatic osteosarcoma at the time of definitive surgery. Patients with lower degree of necrosis have a higher risk of relapse and poor outcome even after chemotherapy and complete resection of the primary tumor. Therefore, a better understanding of the underlying molecular genetic events leading to tumor initiation and progression could result in the identification of potential diagnostic and therapeutic targets. Methods: We used a genome-wide screening method - array based comparative genomic hybridization (array-CGH) to identify DNA copy number changes in 48 patients with osteosarcoma. We applied fluorescence in situ hybridization (FISH) to validate some of amplified clones in this study. Results: Clones showing gains (79%) were more frequent than losses (66%). High-level amplifications and homozygous deletions constitute 28.6% and 3.8% of tumor genome respectively. High-level amplifications were present in 238 clones, of which about 37% of them showed recurrent amplification. Most frequently amplified clones were mapped to 1p36.32 (PRDM16), 6p21.1 (CDC5L, HSPCB, NFKBIE), 8q24, 12q14.3 (IFNG), 16p13 (MGRN1), and 17p11.2 (PMP22 MYCD, SOX1,ELAC27). We validated some of the amplified clones by FISH from 6p12-p21, 8q23-q24, and 17p11.2 amplicons. Homozygous deletions were noted for 32 clones and only 7 clones showed in more than one case. These 7 clones were mapped to 1q25.1 (4 cases), 3p14.1 (4 cases), 13q12.2 (2 cases), 4p15.1 (2 cases), 6q12 (2 cases), 6q12 (2 cases) and 6q16.3 (2 cases). Conclusions: This study clearly demonstrates the utility of array CGH in defining high-resolution DNA copy number changes and refining amplifications. The resolution of array CGH technology combined with human genome database suggested the possible target genes present in the gained or lost clones. © 2004 Man et al; licensee BioMed Central Ltd. |
| Keywords: | osteosarcoma; adolescent; adult; child; clinical article; controlled study; human tissue; preschool child; aged; bone neoplasms; child, preschool; middle aged; bone tumor; unclassified drug; human cell; gene deletion; genetics; methodology; genetic analysis; cell cycle protein; chromosome 12; gene targeting; gene amplification; transcription factor; validation study; chromosomes, human, pair 8; standard; molecular cloning; chromosome aberration; gene mapping; homozygosity; fluorescence in situ hybridization; dna; amplicon; chromosomes, human, pair 6; chromosome aberrations; nucleic acid hybridization; cell clone; chromosome 8; chromosome deletion; genetic screening; comparative genomic hybridization; protein kinase; chromosome 6; clone cells; chromosome 1q; chromosome 17; chromosome 12q; chromosome 3p; chromosome 6q; chromosome 1p; chromosome 8q; chromosome map; chromosome mapping; genetic database; chromosome 17p; chromosomes, human, pair 17; chromosome 16p; chromosome 13q; chromosome 6p; chromosomes, human, pair 12; nucleic acid amplification techniques; nucleic acid amplification; chromosome 4p; humans; human; male; female; article; peripheral myelin protein 22; transcription factor elk 3 |
| Journal Title: | BMC Cancer |
| Volume: | 4 |
| Issue: | 45 |
| ISSN: | 1471-2407 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2004-08-07 |
| Start Page: | 45 |
| Language: | English |
| DOI: | 10.1186/1471-2407-4-45 |
| PROVIDER: | scopus |
| PMCID: | PMC514550 |
| PUBMED: | 15298715 |
| DOI/URL: | |
| Notes: | BMC Cancer -- Cited By (since 1996):75 -- Export Date: 16 June 2014 -- CODEN: BCMAC -- Source: Scopus |
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