Genomic and Expression Analysis of the 8p11–12 Amplicon in Human Breast Cancer Cell Lines

Abstract

Gene amplification is an important mechanism of oncogene activation in breast and other cancers. Characterization of amplified regions of the genome in breast cancer has led to the identification of important oncogenes including erbB-2/HER-2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is amplified in 10 -15% of human breast cancers. The putative oncogene FGFR1 localizes to this region; however, we show evidence that FGFR inhibition fails to slow growth of three breast cancer cell lines with 8p11-p12 amplification. We present a detailed analysis of this amplicon in three human breast cancer cell lines using comparative genomic hybridization, traditional Southern and Northern analysis, and chromosome 8 cDNA microarray expression profiling. This study has identified new candidate oncogenes within the 8p11-p12 region, supporting the hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast cancers with proximal 8p amplification.

High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation

“…Several (Cama-1, HCC1500, MDA-MB-134, MDA-MB-175, MDA-MB-361, SUIT-2, SUM44, SUM52 and ZR-75-1) show at least low-level amplification of a fragment immediately proximal to the main break. All of these, except Cama-1, have been reported before (Lemieux et al, 1996;Courtay-Cahen et al, 2000;Adelaide et al, 2003;Ray et al, 2004;Garcia et al, 2005) and all, except those in Cama-1 and the SUM lines, have been verified by us using FISH with BACs and chromosome 8 paint. HCC38 and UACC812 have a small amplicon substantially proximal to the main break, and two BACs spanning the FGFR1 locus are amplified in HCC1599.…”

“…FGFR1, at 38.4 Mb, although originally proposed as the principle target for amplification in this region, is not included (Ray et al, 2004;Garcia et al, 2005;Prentice et al, 2005). This amplicon we defined using the same array on breast tumour tissues (Garcia et al, 2005), and it was independently identified by Prentice et al (2005).…”

“…large-scale amplifications) attached to 8p12 (Bernardino et al, 1998) and fluorescence in situ hybridization (FISH), CGH and Southern blotting show amplification generally in the region of 8p12 (Dib et al, 1995;Bautista and Theillet, 1998;Davidson et al, 2000), which often, but not invariably, includes FGFR1, and may occasionally extend as far distally as NRG1 (Ugolini et al, 1999). Recent array CGH studies that examine the 8p12 region in breast cancer have concentrated on the definition of the 8p12 amplicon (Ray et al, 2004;Garcia et al, 2005;Prentice et al, 2005). The amplicon has been defined to extend from 36.9 to 37.9 Mb (Garcia et al, 2005).…”

Array comparative genomic hybridization identifies genetic regions associated with outcome in aggressive diffuse large B‐cell lymphomas

“…[8][9][10][11] However, the role of genomic gains or losses in the outcome of patients with DLBCL remains unclear. Thus, the breakpoints at 1q21 and deletions of 6q may be associated with poor outcome, whereas chromosomal-CGH suggests an association between 17p loss and short survival.…”

Multicolour-banding fluorescence in situ hybridisation (mbanding-FISH) to identify recurrent chromosomal alterations in breast tumour cell lines

“…The 8p11 -p21 region contains several potential TSG and oncogenes (Adélaïde et al, 1998(Adélaïde et al, , 2003Ugolini et al, 1999;Conte et al, 2002;Ray et al, 2004).…”