title: Increased copy number at 17q22-q24 by CGH in breast cancer is due to high-level amplification of two separate regions.
abstract: Studies by comparative genomic hybridization (CGH) have defined a chromosomal site at 17q22-q24 that is often overrepresented in breast cancer, neuroblastoma, and several other tumor types. Due to the limited resolution and dynamic range of CGH, it remain unclear whether this gain reflects high-level amplification of small subregion(s) or low-level gain of most of the distal 17q. We used 32 physically mapped 17q probes to construct more accurate copy number profiles for 14 breast cancer cell lines by interphase fluorescence in situ hybridization (FISH). Six cell lines (43%) showed an increased copy number of the 17q-22q24 region by CGH, and seven (50%) by FISH. FISH copy number profiles had a substantially higher dynamic range than did CGH profiles. FISH revealed two independent, highly amplified regions (A and B) at 17q23, separated by about 5 Mb of non-amplified DNA. These regions were distinctly telomeric from the ERBB2 gene locus. However, region A was often co-amplified with ERBB2, whereas B was amplified in cell lines that showed no ERBB2 amplification. We conclude that distal 17q gains recently discovered in breast cancer by CGH are due to high-level amplifications of two different regions at 17q23. This chromosomal region has previously been reported to undergo allelic loss and therefore was thought to harbor a tumor suppressor gene. The present FISH data provide support for the presence, and a starting point for the positional isolation, of 17q23 genes whose upregulation by amplification may play a role in the progression of breast cancer and many other tumor types.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tempere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Bärlund
authors.forename: M
authors.initials: M
authors.lastname: Tirkkonen
authors.forename: F
authors.initials: F
authors.lastname: Forozan
authors.forename: M M
authors.initials: MM
authors.lastname: Tanner
authors.forename: O
authors.initials: O
authors.lastname: Kallioniemi
authors.forename: A
authors.initials: A
authors.lastname: Kallioniemi
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D018628:Gene Dosage; D052138:Genes, Neoplasm; D016147:Genes, Tumor Suppressor; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D014407:Tumor Cells, Cultured
chemical_list: D015342:DNA Probes; D004273:DNA, Neoplasm