Simons A, Schepens M, Jeuken J, Sprenger S, van de Zande G, Bjerkehagen B, Forus A, Weibolt V, Molenaar I, van den Berg E, Myklebost O, Bridge J, van Kessel A G, Suijkerbuijk R
Department of Human Genetics, University Hospital, Nijmegen, The Netherlands.
Cancer Genet Cytogenet. 2000 Apr 15;118(2):89-98. doi: 10.1016/s0165-4608(99)00178-8.
To search for new recurrent genetic aberrations in malignant fibrous histiocytoma (MFH), a combination of conventional cytogenetic, comparative genomic hybridization (CGH), and Southern blot analyses was applied to a series of 34 tumors. Cytogenetic analysis revealed the presence of multiple structural and numerical aberrations, including marker chromosomes, telomeric associations, double minutes, and ring chromosomes. The most frequent genomic imbalances in this series of neoplasms as detected by CGH were gains of 1q21-q22 (69%), 17q23-qter (41%), and 20q (66%), and losses of 9p21-pter (55%), 10q (48%), 11q23-qter (55%), and 13q10-q31 (55%). Southern blot analyses with p16(INK4A) (CDKN2A; 9p21) and RB1 (13q14) probes provided clear indications for frequent deletions of these tumor suppressor genes, and as such, substantiated the CGH results. Additionally, examination of the TP53 and MDM2 genes showed frequent loss and amplification, respectively. These data indicate that genes involved in the RB1- and TP53-associated cell cycle regulatory pathways may play prominent roles in the development of human MFH.
为了寻找恶性纤维组织细胞瘤（MFH）中新的复发性基因畸变，我们将传统细胞遗传学、比较基因组杂交（CGH）和Southern印迹分析相结合，应用于一系列34个肿瘤样本。细胞遗传学分析显示存在多种结构和数量畸变，包括标记染色体、端粒联合、双微体和环状染色体。通过CGH检测，该系列肿瘤中最常见的基因组失衡为1q21-q22（69%）、17q23-末端（41%）和20q（66%）的增益，以及9p21-末端（55%）、10q（48%）、11q23-末端（55%）和13q10-q31（55%）的缺失。用p16（INK4A）（CDKN2A；9p21）和RB1（13q14）探针进行的Southern印迹分析明确显示了这些肿瘤抑制基因的频繁缺失，从而证实了CGH结果。此外，对TP53和MDM2基因的检测分别显示出频繁的缺失和扩增。这些数据表明，参与RB1和TP53相关细胞周期调节途径的基因可能在人类MFH的发生发展中起重要作用。
