High-resolution mapping of a 130-kb core region of the MYCN amplicon in neuroblastomas

被引:32
作者
Reiter, JL [1 ]
Brodeur, GM [1 ]
机构
[1] WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110
关键词
D O I
10.1006/geno.1996.0081
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The MYCN proto-oncogene is amplified in 25% of neuroblastomas, and amplification is strongly correlated with advanced disease stage and with rapid tumor progression. We have generated a high-resolution restriction map of nearly 500 kb spanning the MYCN locus by subcloning yeast artificial chromosomes into cosmids. Cosmids plus additional amplified probes were hybridized to DNA from 33 MYCN amplified neuroblastomas, and we determined that the amplicons range from 350 kb to over 1 Mb. Deletions and rearrangements of the MYCN amplicon occurred less frequently in primary tumors than in cell lines. We have defined a 130-kb region that was amplified in 32 of 33 tumors. One additional tumor deleted 65 kb of this region from its amplicon, while amplifying a large amount of flanking DNA. The only CpG island found in this region was within the MYCN gene, In conclusion, our data demonstrate that, despite the large size of most amplicons, the core domain that is consistently amplified in neuroblastomas probably contains little more than the MYCN gene. (C) 1996 Academic Press, Inc.
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收藏
页码:97 / 103
页数:7
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