Premium
High‐resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays
Author(s) -
Squire Jeremy A.,
Pei Jianming,
Marrano Paula,
Beheshti Ben,
Bayani Jane,
Lim Gloria,
Moldovan Laura,
Zielenska Maria
Publication year - 2003
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10273
Subject(s) - comparative genomic hybridization , biology , gene duplication , genetics , metaphase , copy number analysis , complementary dna , chromosome , copy number variation , microarray , dna microarray , segmental duplication , gene , microbiology and biotechnology , genome , gene family , gene expression
Conventional cytogenetic and comparative genomic hybridization (CGH) studies have shown that osteosarcomas (OSs) are characterized by complex structural and numerical chromosomal alterations and gene amplification. In this study, we used high‐resolution CGH to investigate recurrent patterns of genomic imbalance by use of DNA derived from nine OS tumors hybridized to a 19,200‐clone cDNA microarray. In six OSs, there was copy number gain or amplification of 6p, with a minimal region of gain centering on segment 6p12.1. In seven OSs, the pattern of amplification affecting chromosome arm 8q showed high‐level gains of 8q12–21.3 and 8q22–q23, with amplification of the MYC oncogene at 8q24.2. Seven OSs showed copy number gain or amplification of 17p between the loci bounded by GAS7 and PMI (17p11.2–17p12), and three of these tumors also showed small losses at 17p13, including the region containing TP53 . An in silico analysis of the distribution of segmental duplications (duplicons) in this region identified a large number of tracts consisting of paralogous sequences mapping to the 17p region, encompassing the region of deletions and amplifications in OS. Interestingly, within this same region there were clusters of duplicons and several genes that are expressed during bone morphogenesis and in OS. In summary, microarray CGH analysis of the chromosomal imbalances of OS confirm the overall pattern observed by use of metaphase CGH and provides a more precise refinement of the boundaries of genomic gains and losses that characterize this tumor. © 2003 Wiley‐Liss, Inc.