Malignant astrocytoma‐derived region of common amplification in chromosomal band 17p12 is frequently amplified in high‐grade osteosarcomas
Theo J.M. HulsebosEngelien H. BijleveldNiels T. OskamA. WesterveldSieger LeenstraPancras C.W. HogendoornJohannes Bras
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Abstract:
Recently, we reported a new amplification event that involves marker D17S67 in 17p12 in three malignant astrocytomas of patients with a very short survival. The amplified region may contain an oncogene implicated in astrocytoma tumorigenesis. To determine the extent of the amplified regions, we constructed a yeast artificial chromosome contig spanning the D17S67 region and tested the amplification status of markers that map to the contig. We determined a commonly amplified region between markers D17S1311 and D17S1875 with a maximal length of 1,630 kb. By using marker 745R, from within the commonly amplified region, we screened 60 high-grade astrocytomas but could not detect additional tumors with the amplification event. This suggests that the incidence of the amplification event in high-grade astrocytoma is low (5%). It has recently been shown by comparative genomic hybridization that amplification of 17p11-p12 is a frequent event in high-grade osteosarcomas, occurring in 20–30% of cases. Since the commonly amplified region is within 17p12, we tested 745R in 20 osteosarcomas, including 6 lung metastases, and detected amplification in 9 cases (45%). Marker 745R was found to be amplified in 4 of the 6 lung metastases (66%). From this frequent involvement and the association with clinically aggressive astrocytomas we conclude that for both tumor types presence of the amplification event seems to correlate with aggressive clinical behaviour. Genes Chromosom. Cancer 18:279–285, 1997. © 1997 Wiley-Liss, Inc.Keywords:
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Abstract Brain tumors are the second most common childhood cancer. We used high‐resolution array comparative genomic hybridization (aCGH) to analyze losses and gains of genetic material from 24 medulloblastomas. The bacterial artificial chromosome clones were ordered on the array, allowing for an average resolution of approximately 420 kilobases. The advantage of this high resolution is that the breakpoints associated with subregional chromosome copy number aberrations can be accurately defined, which in turn allows candidate genes within these regions to be readily defined. In this analysis, we confirmed the frequent involvement of loss of 17p and gain of 17q, although we have now established the position of the breakpoint that consistently lies in the chr17:18318880–19046234 region of the chromosome. Other frequent losses were seen on 8p, 10q, 16q, and 20p, and frequent gains were seen on 2p, 4p, 7, and 19. In addition, the fine‐resolution mapping provided by aCGH made it possible to define small chromosome deletions in 1q23.3–q24.2, 2q13.12–q13.2, 6q25–qter, 8p23.1, 10q25.1, and 12q13.12–q13.2. Overall, amplification events were rare, the most common involving MYC (16%), on 8q, although isolated events were seen in 10p11 and 3q. © 2005 Wiley‐Liss, Inc.
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