Low frequency of alterations of the α (PPP2R1A) and β (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms
Low frequency of alterations of the α (PPP2R1A) and β (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms
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DOI：
10.1038/sj.onc.1203389
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发表时间：
2000-02-24
期刊：
影响因子：
8
通讯作者：
Negrini, M
中科院分区：
文献类型：
--
作者：
Calin, GA;di Iasio, MG;Negrini, M
磷酸酶2A(PP2A)是一种主要的细胞丝氨酸-苏氨酸磷酸酶，最近发现其亚基A的β亚型PPP2R1B的编码基因在人类肺癌和结直肠癌中发生了改变，提示其在人类肿瘤发生中的作用。本文报道了乳腺癌、肺癌和黑色素瘤中α(PPP2R1A)和β亚型基因的突变的检测结果，其中4例乳腺癌中发现了影响PPP2R1B的突变，而乳腺癌、肺癌和1例黑色素瘤中发现了PPP2R1B的突变。影响PPP2R1B的突变多为外显子缺失，提示剪接异常。这些剪接异常在缺乏正常剪接产物的肿瘤样本中被检测到，并且在几个正常对照中没有发现。在一个病例中，肿瘤DNA中存在纯合子缺失，而匹配的正常对照中没有。影响PPP2R1A基因的突变包括核苷酸替换、改变高度保守的氨基酸和一次移码。尽管改变的频率很低，但在人类癌症突变的基因中包含A亚基的两种异构体，以及将乳腺癌添加到PPP2R1B改变的肿瘤列表中，加强了PP2A在人类肿瘤发生中的潜在作用。
The phosphatase 2A (PP2A) is one of the major cellular serine-threonine phosphatases, It was recently shown that the gene encoding for the beta isoform of its subunit A, PPP2R1B, is altered in human lung and colorectal carcinomas, suggesting a role in human tumorigenesis, Here, we report the detection of mutations in breast, lung carcinomas and melanomas in the genes of both alpha (PPP2R1A) and beta isoforms, Mutations affecting PPP2R1B were found in four breast carcinomas, while mutations in PPP2R1A were found in carcinomas of the breast and of the lung and in one melanoma. Most of the mutations affecting PPP2R1B were exons deletions, suggesting abnormal splicing. These splicing abnormalities were detected in tumor samples in the absence of the normal splicing product, and were not found in several normal controls. In one case, a homozygous deletion present in tumor DNA, and not in the matched normal control was demonstrated. Mutations affecting the PPP2R1A gene were nucleotide substitutions changing highly conserved amino acids and one frame-shift. Although the frequency of alterations is low, the inclusion of both isoforms of subunit A in the genes mutated in human cancer and the addition of breast cancer to the list of neoplasms in which PPP2R1B is altered, strengthen the potential role of PP2A in human tumorogenesis.