耿源源①, 陈 玥, 赵稳兴, 王 丽, 王 力, 杨举伦. 乳腺良恶性病变GSTP1 基因的突变和多态性分析*[J]. 中国肿瘤临床, 2010, 37(18): 1028-1031. DOI: 10.3969/j.issn.1000-8179.2010.18.003
引用本文: 耿源源①, 陈 玥, 赵稳兴, 王 丽, 王 力, 杨举伦. 乳腺良恶性病变GSTP1 基因的突变和多态性分析*[J]. 中国肿瘤临床, 2010, 37(18): 1028-1031. DOI: 10.3969/j.issn.1000-8179.2010.18.003
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GENG Yuanyuan, CHEN Yue, ZHAO Wenxing, WANG Li, WANG Li, YANG Julun. Mutations and Polymorphisms of GSTP1 Gene in Benign and Malignant Breast Lesions[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(18): 1028-1031. DOI: 10.3969/j.issn.1000-8179.2010.18.003
Citation: GENG Yuanyuan, CHEN Yue, ZHAO Wenxing, WANG Li, WANG Li, YANG Julun. Mutations and Polymorphisms of GSTP1 Gene in Benign and Malignant Breast Lesions[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(18): 1028-1031. DOI: 10.3969/j.issn.1000-8179.2010.18.003
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乳腺良恶性病变GSTP1 基因的突变和多态性分析*

Mutations and Polymorphisms of GSTP1 Gene in Benign and Malignant Breast Lesions

    摘要
  • 摘要: 目的：检测谷胱甘肽S-转移酶P1（glutathione S-transferase P 1，GSTP1）基因各外显子的突变和多态性，探讨其与乳腺癌发生的关系。方法：选取乳腺癌及其相应癌旁增生组织标本各50例，良性增生组织标本50例，正常乳腺组织50例和正常人（志愿者）血液淋巴细胞15例为研究对象，运用PCR-SSCP 技术和DNA测序的方法检测GSTP1 基因外显子突变和多态性。结果：1）在3/50例（6%）乳腺癌组织中检测到GSTP1 基因外显子3 的11个位点发生突变，其中8 个突变位点是错义突变（MS），均可导致氨基酸的改变；2 个突变位点是同义突变（SS），氨基酸未发生改变；1 个突变位点发生移码突变（FS），造成氨基酸读码框顺序的改变，并产生新的终止密码子，使蛋白发生截短，造成功能缺失。在5/50例（10%）乳腺癌组织中检测到外显子4 的12个位点发生突变，其中6 个为错义突变（MS），均可导致氨基酸的改变；6 个移码突变（FS），突变热点在221 位碱基，发生率最高（33%）。 外显子6、7 和剪接点未见突变。在正常人外周血淋巴细胞、正常乳腺组织、癌旁和非癌旁乳腺增生组织中均未检测到该基因突变。2）在12/50例（24%）乳腺癌，5/50例（10%）乳腺癌旁增生，3/50例（6%）乳腺良性增生，3/50例（6%）正常乳腺组织和1/15例（6.7%）正常人淋巴细胞检测到GSTP1 基因外显子5 第313 核苷酸多态性（A→G，导致Ile105Val）。 结论：研究结果提示：1）GSTP1 基因外显子突变可能与部分乳腺癌的发生有关；2）GSTP1 第5 外显子的多态性与乳腺癌易感性可能有关。

     

    Abstract: Objective:To investigate the role of the GSTP 1 gene in the development of breast cancer by detecting the mutations and polymorphisms of GSTP 1 exons in breast benign and malignant lesions. Methods:Fresh tissue samples from 50breast cancer cases, 50adjacent hyperplastic cases, 50benign hyperplasia cases,50 normal breast tissue sam-ples, as well as 15samples of normal peripheral blood lymphocytes were used to detect mutations and polymorphisms of GSTP1 exons using PCR-SSCP and DNA sequencing.Results: GSTP1 exon3 mutations were detected in3 of 50(16%) breast cancer cases, of which 11sites exhibited changes: 8 sites consisted of missense (MS) mutations, which can result in changes to amino acids; 1 site consisted of a frameshift (FS) mutation, which can result in a shift of the reading frame se-quence, changing the amino acids and producing a new stop codon, resulting in loss of function. Exon4 mutations were de-tected in 5 of 5(10%) breast cancer cases, of which 12sites were changed: 6 sites were MS mutations and6 sites were FS mutations. The hot spot or highest incidence of mutation was found at 221 bases (33%). No mutations were found in ex-on6, exon 7 or splice junctions. GSTP1 mutations were not found in any adjacent hyperplastic tissue, benign hyperplasia tissue or normal breast tissue. Single nucleotide polymorphism (A→G, leading to Ile105 Val) of exon5 was detected in 12of
    50(24%) breast cancer tissues,5 of 50(10%) adjacent hyperplasia tissues,3 of 50(6%) benign hyperplasia tissues, 5 of 50(10%) normal breast tissues, and1 of 15(6.7%) normal peripheral blood lymphocytes.Conclusion : It is suggested that the mutation of GSTP 1 gene is associated with the development of partial breast cancers. The polymorphism frequency of GSTP1 in exon 5 is not compatible with other factors in cancer, precancerous lesions and controls, the highest frequency was found in cancer cases. The structural abnormity of GSTP1 is varied. It will be helpful to future research to illustrate the relationship between gene mutations and the function of GSTP 1 in the tumorigenesis of breast cancer.

     

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