INCREASED COPY NUMBER AT 17Q22-Q24 BY CGH IN BREAST-CANCER IS DUE TO HIGH-LEVEL AMPLIFICATION OF 2 SEPARATE REGIONS

Studies by comparative genomic hybridization (CGH) have defined a chro mosomal site at 17q22-q24 that is often overrepresented in breast canc er, neuroblastoma, and several other tumor types. Due to the limited r esolution and dynamic range of CGH, it remains unclear whether this ga in reflects high-level amplification of small subregion(s) or low-leve l gain of most of the distal 17q. We used 32 physically mapped 17q pro bes to construct more accurate copy number profiles for 14 breast canc er cell lines by interphase fluorescence in situ hybridization (FISH). Six cell lines (43%) showed an increased copy number of the 17q22-q24 region by CGH, and seven (50%) by FISH. FISH copy number profiles had a substantially higher dynamic range than did CGH profiles. FISH reve aled two independent, highly amplified regions (A and B) at 17q23, sep arated by about 5 Mb of non-amplified DNA, These regions were distinct ly telomeric from the ERBB2 gene locus. However, region A was often co -amplified with ERBB2, whereas B was amplified in cell lines that show ed no ERBB2 amplification. We conclude that distal 17q gains recently discovered in breast cancer by CGH are due to high-level amplification s of two different regions at 17q23. This chromosomal region has previ ously been reported to undergo allelic loss and therefore was thought to harbor a tumor suppressor gene. The present FISH data provide suppo rt for the presence, and a starting point for the positional isolation , of 17q23 genes whose upregulation by amplification may play a role i n the progression of breast cancer and many other tumor types. (C) 199 7 Wiley-Liss, Inc.