Tumor-suppressive pathways in pancreatic carcinoma.
Tumor-suppressive pathways in pancreatic carcinoma.
复制标题
DOI：
--
复制
发表时间：
1997-05
期刊：
影响因子：
11.2
通讯作者：
E. Rozenblum;M. Schutte;M. Goggins;S. Hahn;Shawn Panzer;M. Zahurak;S. Goodman;T. Sohn;R. Hruban;C. Yeo;S. Kern
中科院分区：
文献类型：
--
作者：
E. Rozenblum;M. Schutte;M. Goggins;S. Hahn;Shawn Panzer;M. Zahurak;S. Goodman;T. Sohn;R. Hruban;C. Yeo;S. Kern
在肿瘤发生过程中，正选择作用于那些改变限速调节途径的肿瘤细胞。这一原理的一个推论是，一个基因的突变消除了在同一途径中改变另一个基因的需要，并且不同基因突变在单个肿瘤中的共存意味着它们参与不同的肿瘤抑制途径。我们研究了42例胰腺癌中K-ras癌基因和p16、p53和DPC 4肿瘤抑制基因的遗传改变。他们都有K-ras基因突变。38%的肿瘤有4个改变的基因，另外38%有3个改变的基因，15%有2个改变的基因，8%的肿瘤有1个改变的基因。有趣的是，我们注意到DPC 4和p16失活的高度一致性（P = 0.007），这表明p16的遗传失活增加了DPC 4随后突变的选择优势。这些癌症基因的改变与病理或临床参数之间没有统计学显著相关性。在人类肿瘤中的这种类型的多基因分析可能有助于证实实验肿瘤模型，从而增加我们对在人类肿瘤发生过程中被废除的真正生理相关的肿瘤抑制途径的理解。
During tumorigenesis, positive selection is exerted upon those tumor cells that alter rate-limiting regulatory pathways. A corollary of this principle is that mutation of one gene abrogates the need for alteration of another gene in the same pathway and also that the coexistence in a single tumor of mutations in different genes implies their involvement in distinct tumor-suppressive pathways. We studied 42 pancreatic adenocarcinomas for genetic alterations in the K-ras oncogene and the p16, p53, and DPC4 tumor suppressor genes. All of them had the K-ras gene mutated. Thirty-eight % of the tumors had four altered genes, another 38% had three altered genes, 15% had two altered genes, and 8% of the tumors had one altered gene. Interestingly, we noted a high concordance of DPC4 and p16 inactivations (P = 0.007), suggesting that the genetic inactivation of p16 increases the selective advantage of subsequent mutation in DPC4. No statistically significant association was identified between the alteration of these cancer genes and pathological or clinical parameters. This type of multigenic analysis in human tumors may serve to substantiate experimental tumor models and thus increase our understanding of the truly physiologically relevant tumor-suppressive pathways that are abrogated during human tumorigenesis.