Shao Yi, Sun Zhen-Yuan, Sun Shi-Wei, Zhao Yi, Sin Wan Yee, Yuan Yan-Hua, Simpson Andrew J, Old Lloyd J, Sang Xin-Ting, Mao Yi-Lei, Xie Yong, Huang Jie-Fu, Zhao Hai-Tao
Department of liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, CAMS & PUMC, Beijing 100730, China.
J Cancer Res Clin Oncol. 2008 Apr;134(4):495-502. doi: 10.1007/s00432-007-0312-z. Epub 2007 Sep 25.
The purpose of this study is to identify single nucleotide polymorphisms (SNPs) in the coding region alleles of the X chromosomal LAGE-1 gene, and investigate the frequency of such SNPs in both cancer patients and healthy controls, and thus determine the potential significance of these SNPs with respect to cancer vaccine therapy.
In this study, different mRNAs transcribed from the LAGE-1 gene were identified by RT-PCR from healthy donors and cancer patients samples.
A new LAGE-1 allele containing three coding region SNPs (69A/G, 317C/G, and 397T/G) were identified. The allele is highly expressed as the LAGE-1a mRNA variant AY679089 in some of the cancer patients. The three SNPs altered the LAGE-1 gene sequence to that of NYESO-1 at both the nucleotide and amino acid level.
There is a high frequency of the LAGE-1 gene allele with SNPs in coding regions in cancer patients. There was a clear relationship between the variant AY679089 and gastric cancer. The SNPs may lead to accelerated progress of poorly differentiated gastric cancer. The SNPs found in these alleles may also alter the immunological characteristics of LAGE-1a and should be taken into account if this antigen is adopted as a cancer vaccine component.
本研究旨在鉴定X染色体LAGE-1基因编码区等位基因中的单核苷酸多态性（SNP），调查这些SNP在癌症患者和健康对照中的频率，从而确定这些SNP在癌症疫苗治疗方面的潜在意义。
在本研究中，通过逆转录聚合酶链反应（RT-PCR）从健康供体和癌症患者样本中鉴定出从LAGE-1基因转录的不同信使核糖核酸（mRNA）。
鉴定出一个新的LAGE-1等位基因，其包含三个编码区SNP（69A/G、317C/G和397T/G）。在一些癌症患者中，该等位基因作为LAGE-1a mRNA变体AY679089高度表达。这三个SNP在核苷酸和氨基酸水平上均将LAGE-1基因序列改变为NYESO-1的序列。
癌症患者中编码区具有SNP的LAGE-1基因等位基因频率较高。变体AY679089与胃癌之间存在明确关联。这些SNP可能导致低分化胃癌进展加速。在这些等位基因中发现的SNP也可能改变LAGE-1a的免疫学特性，如果将该抗原用作癌症疫苗成分，则应予以考虑。
