High-level amplification at 17q23 leads to coordinated overexpression of multiple adjacent genes in breast cancer

Abstract

Increased copy numbers of 17q23 chromosomal region have been shown to occur in different tumour types and to be associated with tumour progression and with poor prognosis. Several genes have earlier been proposed as potential oncogenes at this region largely on the grounds of cell lines studies. In this study, we performed a systematic gene expression survey on 26 primary breast tumours with known 17q23 amplification status by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The 17q23 amplicon is restricted to an B5 MB region in breast cancer and contains 29 known genes. Our survey revealed a statistically significant (Po0.01) difference between the high level and no amplification groups in a set of eleven genes whereas no difference between the moderate and the non-amplified tumour groups were observed. Interestingly, these 11 genes were located adjacent to one another within a 1.56 Mb core region in which all except one of the genes were overexpressed. These data suggest that only high-level amplification at the 17q23 amplicon core leads to elevated gene expression in breast cancer. Moreover, our results highlight the fact that 17q23 amplicon carries multiple candidate genes and that this may be a more common event in gene amplification than previously thought.

High‐resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx

“…We observed that 9% to 64% of genes located in the regions had associated overexpression. This is in line with other studies reporting that highly amplified regions contain a number of overexpressed genes (Hyman et al, 2002;Garcia et al, 2005;Parssinen et al, 2007). In concordance with our data, Snijders et al (2005) detected narrow amplifications at 6q12 (PTP4A1, EGFL11), 9p13.3 (TLN1), 9p24.1 (UHRF2, JMJD2C, PTPRD), and 11p13 (CD44, FJX1, TRAF6) in oral SCC (OSCC) using BAC arrays and confirmed the expression levels of selected genes using Q-RT-PCR.…”

Gene expression meta-analysis identifies chromosomal regions and candidate genes involved in breast cancer metastasis

“…The 17q23-q25 neighboring region can be divided into two regions, 17q21-23 and 17q25, by sliding mean analysis. The 17q21-23 region coincides with a core amplicon identified in breast tumors compared to normal tissue [27]. 20q13 amplification has been associated with poor prognosis [28] and has been validated in several studies [29] while 20q11 gain has not previously been reported to have prognostic meaning independent of 20q13.…”

Genomic Differences Between Pure Ductal Carcinoma In Situ of the Breast and that Associated with Invasive Disease: a Calibrated aCGH Study

“…RPS6KB1, PAT1, and TBX2 were also found coamplified in 10% of tumors (41). A recent study of primary breast tumors revealed that overexpression of 11 genes in the region of 54.5 to 56.1 Mb (FAM33A, DHX40, CLTC, PTRH2, TMEM49, TUBD1, RPS6KB1, ABC1, USP32, APPBP2, and PPMD1) is activated by high level of amplification and was not observed with low-level copy number gain (42). These data are in agreement with our finding that, although gain in the region was common (by moving average), only distinct amplification detectable by the segmentation algorithm was associated with prognostic variables.…”