Latil A, Fournier G, Cussenot O, Lidereau R
Laboratoire d'Oncogénétique, Centre René Huguenin, St-Cloud, France.
J Urol. 1996 Dec;156(6):2079-83.
It is widely accepted that an accumulation of genetic alterations plays an important role in the genesis of human cancers. We wished to obtain a comprehensive view of the role of genetic changes in prostate cancer.
We screened 42 primary prostate tumors for allelic imbalance (AI) on 8 autosomal chromosome arms of interest (5q, 7q, 8p, 10q, 13q, 16q, 17q, 18q) by using 2 DNA probes for restriction fragment length polymorphism (RFLP) and 19 microsatellite markers (CA repeats).
The most frequent allelic imbalances were observed on 8p (58%) and 16q (53%). AI exceeding 20% was also observed at sites on chromosome arms 7q (46%), 10q (23%), 13q (26%), 17q (34%) and 18q (39%), whereas AI was infrequent on 5q (10%).
The data indicate that a relatively large number of chromosome loci play a part in the etiology and progression of this tumor type. Moreover, our findings suggest that inactivation of a putative tumor suppressor gene on 7q and 13q is an early event in prostate tumorigenesis. In contrast, the close link between an invasive phenotype and AI on 10q and 18q suggests that these genetic alterations occur late in prostate tumorigenesis.
人们普遍认为,基因改变的积累在人类癌症的发生中起着重要作用。我们希望全面了解基因变化在前列腺癌中的作用。
我们使用2种用于限制性片段长度多态性(RFLP)的DNA探针和19个微卫星标记(CA重复序列),对42例原发性前列腺肿瘤在8条感兴趣的常染色体臂(5q、7q、8p、10q、13q、16q、17q、18q)上进行等位基因不平衡(AI)筛查。
在8p(58%)和16q(53%)上观察到最常见的等位基因不平衡。在染色体臂7q(46%)、10q(23%)、13q(26%)、17q(34%)和18q(39%)的位点上也观察到AI超过20%,而在5q上AI较少见(10%)。
数据表明,相对大量的染色体位点在这种肿瘤类型的病因学和进展中起作用。此外,我们的研究结果表明,7q和13q上一个假定的肿瘤抑制基因的失活是前列腺肿瘤发生的早期事件。相比之下,侵袭性表型与10q和18q上的AI之间的密切联系表明,这些基因改变发生在前列腺肿瘤发生的晚期。