An AC-repeat adjacent to mouse Cdkn2B allows the detection of specific allelic losses in the p15INK4b and p16INK4a tumor suppressor genes.
An AC-repeat adjacent to mouse Cdkn2B allows the detection of specific allelic losses in the p15INK4b and p16INK4a tumor suppressor genes.
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与小鼠 Cdkn2B 相邻的 AC 重复允许检测 p15INK4b 和 p16INK4a 肿瘤抑制基因中的特定等位基因丢失。
DOI：
10.1007/s003359900722
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Pellicer,A
中科院分区：
文献类型：
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作者：
Malumbres,M;PérezdeCastro,I;Santos,J;Pérez-Ollé,R;Fernández-Piqueras,J;Pellicer,A
细胞周期蛋白依赖性激酶抑制剂sp15INK4bandp16INK4a参与多种人类和小鼠肿瘤的发生。这些肿瘤抑制基因通常因编码区点突变或其启动子高甲基化相关的缺失而失活。在这项工作中，我们描述了位于小鼠第 4 号染色体 (Chr) 中 Cdkn2B (p15INK4b) 和 Cdkn2A (p16INK4a) 基因之间的简单序列长度多态性，仅位于 Cdkn2 基因座下游 700 bp 处。在不同的近交系中对该 DNA 区域进行了分析，显示出可变的 AC 重复 DNA 序列。我们使用该微卫星检测 γ 辐射诱导的 C57BL/6J × RF/J F1 杂种胸腺淋巴瘤中 Cdkn2A 和 Cdkn2Bloci 杂合性的丧失。使用这种特定的标记，我们能够定位其他微卫星未检测到的其他等位基因丢失。由于等位基因丢失可以通过简单的 PCR 扩增来检测，因此该 AC 重复序列特别可用作这些 Cdkn2 基因的遗传标记，特别适用于 p15INK4b 细胞周期抑制剂。
The cyclin-dependent kinase inhibitorsp15INK4bandp16INK4aare involved in the development of a wide range of human and murine tumors. These tumor suppressor genes are inactivated by deletions frequently associated to point mutations in the coding regions or hypermethylation of their promoters. In this work, we describe a simple-sequence length polymorphism located in mouse Chromosome (Chr) 4, between theCdkn2B(p15INK4b) andCdkn2A(p16INK4a) genes, only 700 bp downstream of theCdkn2Blocus. This DNA region was analyzed in different inbred strains showing a variable AC-repetitive DNA sequence. We used this microsatellite to detect loss of heterozygosity of theCdkn2AandCdkn2Bloci in γ-irradiation-induced thymic lymphomas of C57BL/6J × RF/J F1hybrids. Using this specific marker, we were able to locate additional allelic losses not detected by other microsatellites. Since the allelic losses can be detected by a simple PCR amplification, this AC-repetitive sequence is specially useful as a genetic marker for theseCdkn2genes and specifically for thep15INK4bcell cycle inhibitor.