High-resolution cDNA microarray CGH mapping of genomic imbalances in osteosarcoma using formalin-fixed paraffin-embedded tissue.
Formalin-fixed paraffin embedded (FFPE) tumor tissue provides an opportunity to perform retrospective genomic studies of tumors in which chromosomal imbalances are strongly associated with oncogenesis. The application of comparative genomic hybridization (CGH) has led to the rapid accumulation of cytogenetic information on osteosarcoma (OS); however, the limited resolving power of metaphase CGH does not permit precise mapping of imbalances. Array CGH allows quantitative detection and more precise delineation of copy number aberrations in tumors. Unfortunately the high cost and lower density of BACs on available commercial arrays has limited the ability to comprehensively profile copy number changes in tumors such as OS that are recurrently subject to genomic imbalance. In this study a cDNA/EST microarray including 18,980 human cDNAs (which represent all 22 pairs of autosomal chromosomes and chromosome X) was used for CGH analysis of eight OS FFPE. Chromosomes 1, 12, 17, and X harbored the most imbalances. Gain/amplification of X was observed in 4/8 OS, and in keeping with other recent genomic analyses of OS, gain/amplification of 17p11.2 was often accompanied by a distal deletion in the region of the p53 gene. Gain/amplification of the X chromosome was verified using interphase FISH carried out on a subset of OS FFPE sections and OS tissue arrays.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Princess Margaret Hospital and The Ontario Cancer Institute, Ont, Canada.
M
M
Zielenska
P
P
Marrano
P
P
Thorner
J
J
Pei
B
B
Beheshti
M
M
Ho
J
J
Bayani
Y
Y
Liu
B C
BC
Sun
J A
JA
Squire
X-S
XS
Hao
D000293:Adolescent; D002648:Child; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005557:Formaldehyde / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007399:Interphase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012516:Osteosarcoma / Q000235:genetics*; D016612:Paraffin Embedding / Q000379:methods*; D016707:Tissue Fixation / Q000379:methods*
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D005557:Formaldehyde