Corvi R, Savelyeva L, Breit S, Wenzel A, Handgretinger R, Barak J, Oren M, Amler L, Schwab M
Division of Cytogenetics, German Cancer Research Center, Heidelberg.
Oncogene. 1995 Mar 16;10(6):1081-6.
Amplification of the MYCN gene is a well documented genetic alteration of aggressively growing human neuroblastomas. Through cytogenetic studies we have identified neuroblastoma cell lines which, in addition to amplified MYCN, carry amplified DNA not harbouring MYCN. In situ hybridization of biotinylated total genomic DNA to metaphase chromosomes of normal human lymphocytes by reverse genomic hybridization revealed the amplified DNA to be derived from chromosome 12 band q13-14. Subsequent filter analyses showed a 20- to 40-fold amplification of the MDM2 gene, located at 12q13-14, both in three cell lines and in an original tumor, in addition to amplified MYCN. As the apparent consequence of amplification abundant MDM2 protein was present, a part of which was complexed with p53.
MYCN基因的扩增是侵袭性生长的人类神经母细胞瘤中一种有充分文献记载的基因改变。通过细胞遗传学研究，我们鉴定出了神经母细胞瘤细胞系，这些细胞系除了MYCN基因扩增外，还携带不含MYCN的扩增DNA。通过反向基因组杂交，将生物素化的全基因组DNA与正常人淋巴细胞的中期染色体进行原位杂交，结果显示扩增的DNA来源于12号染色体q13 - 14带。随后的滤膜分析表明，位于12q13 - 14的MDM2基因在三个细胞系和一个原发肿瘤中除了MYCN基因扩增外，还出现了20至40倍的扩增。作为扩增的明显结果，存在大量的MDM2蛋白，其中一部分与p53形成复合物。
