Novel amplification and deletions in osteosarcomas detected by comparative genomic hybridization

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:133531

Knuutila, S; Tarkkanen, M ^[1]; Karhu, R ^[2]

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1. Univ. of Helsinki (Finland)
2. Tampere Univ. Hospital (Finland); and others

Genetic changes underlying the initiation and progression of osteosarcomas are poorly known. We have used a recently developed method, comparative genomic hybridization (CGH) to study genetic changes in 11 osteosarcomas. CGH is a powerful method that allows detection of DNA sequence copy number changes (losses, deletions, gains and amplifications) along the genome. In CGH differentially labeled tumor and normal DNA are hybridized to normal metaphase spreads. Losses and gains are detected as changes is the relative fluorescence intensity ratio and are quantitated by digital imaging. The material consisted of two parosteal osteosarcomas, eight grade II or IV primary osteosarcomas and one grade IV pulmonary metastasis. CGH showed that osteosarcomas are genetically extremely complex as the mean number of aberrations per tumor was 11 (range one to 20 per tumor). The most common (45-36%) gains were detected at 1q, 8q (not the myc-locus), 11q and X. The most common (36%) losses were detected at 2q, 6q, and 10p. High-level amplifications were seen in seven tumors at several small regions, e.g. 12q12-14 (the SAS-MDM2 locus) and 17p11.2-12. In conclusion, CGH proved to be a useful tool for analysis of DNA sequence copy number changes in osteosarcomas, where conventional cytogenetic analysis is difficult. Several chromosomal regions that have previously not been found out to undergo losses or contain gains of DNA sequences were detected. These regions are likely to contain tumor suppressor genes and oncogenes that play an important role in the development of osteosarcomas.

• OSTI ID: 133531
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMAL ABERRATIONS
DETECTION
DNA HYBRIDIZATION
DNA SEQUENCING
FLUORESCENCE
GENE AMPLIFICATION
GENE MUTATIONS
GENETIC MAPPING
HUMAN CHROMOSOMES
ONCOGENES
OSTEOSARCOMAS
PATIENTS
RESOLUTION