MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas
MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas
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MDM2 扩增以及 Rb 和 p53 基因杂合性丧失：脂肪肉瘤的肿瘤发生没有同时改变
DOI：
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发表时间：
1998
影响因子：
3.6
通讯作者：
A. Roessner
中科院分区：
文献类型：
--
作者：
R. Schneider;H. Walter;K. Radig;J. Ryš;A. Bosse;C. Kuhnen;C. Hoang‐Vu;A. Roessner
目的：研究45例脂肪肉瘤中MDM 2、Rb和p53基因的改变情况。此外，还研究了与组织学和临床参数的可能相关性。方法：以人MDM 2 cDNA为探针，采用非放射性Southern杂交检测MDM 2基因的扩增。采用聚合酶链反应/单链构象多态性分析和直接测序法检测p53基因突变。为了研究肿瘤抑制基因Rb和p53的杂合性丢失（洛），我们使用了4个多态性基因内Rb标记（内含子1、17、20和25）和2个p53标记（内含子1和外显子4）。结果：45例脂肪肉瘤中有19例（42.2%）存在MDM 2扩增。Rb和p53的洛频率几乎相同（22%）。在9例洛肿瘤中的4例（44.4%）中，等位基因丢失是两个基因的并发事件。在45例脂肪肉瘤中，6例（13.3%）存在p53突变。总的来说，45例脂肪肉瘤中有30例（66.6%）发生了p53/MDM 2/Rb通路的改变。与黏液样和多形性变异体不同，分化良好的脂肪肉瘤的特征是MDM 2扩增频率高，Rb和p53缺失洛，以及p53突变。结论：显然，在脂肪肉瘤的肿瘤发生中，MDM 2扩增和Rb和p53基因的洛并不同时发生，而MDM 2扩增和p53基因突变（有一个例外）也是如此。我们认为高分化、粘液样和多形性脂肪肉瘤的特征在于不同的分子改变模式。
Purpose: The present study aimed to investigate the status of alterations of the MDM2, Rb and p53 genes in a series of 45 liposarcomas. Furthermore, the possible correlation with histological and clinical parameters was studied. Methods:MDM2 amplification was examined by non-radioactive Southern blot hybridization with a human MDM2 cDNA probe. Mutations in the p53 gene were screened by polymerase chain reaction/single-strand conformation polymorphism analysis and direct sequencing. To study loss of heterozygosity (LOH) at the tumor-suppressor genes Rb and p53, we used four polymorphic intragenic Rb markers (introns 1, 17, 20, and 25) and two p53 markers (intron 1 and exon 4). Results:MDM2 amplification was found in 19 of 45 liposarcomas (42.2%). The frequency of LOH in Rb and p53 was nearly identical (22%). In 4 of 9 tumors (44.4%) with LOH, allelic loss was a concurrent event in both genes. Of 45 liposarcomas, 6 (13.3%) showed p53 mutations. Overall, alterations of the p53/MDM2/Rb pathway occurred in 30 of 45 liposarcomas (66.6%). In contrast to myxoid and pleomorphic variants, well-differentiated liposarcomas were characterized by a high frequency of MDM2 amplification, a lack of LOH of Rb and p53, and p53 mutations. Conclusions: Obviously MDM2 amplification and LOH at the Rb and p53 genes do not occur simultaneously in the oncogenesis of liposarcomas, as is the case for MDM2 amplification and p53 gene mutations (with one exception). We suggest that well-differentiated, myxoid and pleomorphic liposarcomas are characterized by a different pattern of molecular alterations.
影响因子：
11.2
作者：
D. Brachman;D. Hallahan;M. Beckett;D. Yandell;R. Weichselbaum
通讯作者：
D. Brachman;D. Hallahan;M. Beckett;D. Yandell;R. Weichselbaum
影响因子：
11.2
作者：
F. Leach;T. Tokino;T. Tokino;Paul A. Meltzer;M. Burrell;J. Oliner;Sharon Smith;D. Hill;D. Sidransky;K. Kinzler;B. Vogelstein
通讯作者：
F. Leach;T. Tokino;T. Tokino;Paul A. Meltzer;M. Burrell;J. Oliner;Sharon Smith;D. Hill;D. Sidransky;K. Kinzler;B. Vogelstein
软组织肿瘤中的染色体畸变。
DOI：
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发表时间：
1994
期刊：
The American journal of pathology
影响因子：
--
作者：
Sreekantaiah,C;Ladanyi,M;Rodriguez,E;Chaganti,RS
通讯作者：
Chaganti,RS