Muleris M, Almeida A, Dutrillaux A M, Pruchon E, Vega F, Delattre J Y, Poisson M, Malfoy B, Dutrillaux B
CNRS URA 620, Institut Curie, Section de Biologie, Paris, France.
Oncogene. 1994 Sep;9(9):2717-22.
Nine cases of malignant gliomas were selected for the presence of double minutes (dmin) or homogeneously staining regions (hsr) detected by conventional cytogenetics. Analyses were performed on fresh (2 cases) or xenografted (5 cases) tumors or both (2 cases). A modified comparative genomic hybridization technique (mCGH) was applied exhibiting a single amplified locus in 8 tumors and 4 amplified loci in one tumor. Recurrent sites of amplification were detected in 7p11-p12 (5 cases) and 1q32.1 (2 cases). Signals were also observed in 4q11-q12, 5p15.1, 7q31, 8q24.1 and 9p2 in one tumor each. Southern blotting demonstrated that the genes for EGFR (epidermal growth factor receptor), PDGFRA (platelet derived growth factor receptor alpha), MET and MYC oncogenes were involved in 7p11-p12, 4q11-q12, 7q31 and 8q24.1 amplifications, respectively. These amplifications were found by in situ hybridization on tumor spreads, in dmin or episomes for EGFR, dmin for PDGFRA and MET, and hsr and dmin for MYC genes. Other mCGH signals, for which no target genes could be proposed, were confirmed by chromosome paintings on tumor metaphases. In one of the tumors, the coamplification of DNA from 5p15.1 and 9p2 bands in the same dmin was demonstrated.
选取9例经传统细胞遗传学检测发现存在双微体（dmin）或均匀染色区（hsr）的恶性胶质瘤病例。对新鲜肿瘤组织（2例）、异种移植肿瘤组织（5例）或两者（2例）进行分析。应用改良的比较基因组杂交技术（mCGH），结果显示8例肿瘤有一个扩增位点，1例肿瘤有4个扩增位点。在7p11 - p12（5例）和1q32.1（2例）检测到反复出现的扩增位点。在4q11 - q12、5p15.1、7q31、8q24.1和9p2各有1例肿瘤观察到信号。Southern印迹法表明，表皮生长因子受体（EGFR）、血小板衍生生长因子受体α（PDGFRA）、MET和MYC癌基因分别参与了7p11 - p12、4q11 - q12、7q31和8q24.1的扩增。这些扩增通过肿瘤涂片原位杂交发现，EGFR在dmin或附加体中，PDGFRA和MET在dmin中，MYC基因在hsr和dmin中。其他无法提出靶基因的mCGH信号通过肿瘤中期染色体描绘得到证实。在其中1例肿瘤中，证明了5p15.1和9p2带的DNA在同一dmin中共扩增。
