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. 2008 Apr;134(4):495-502.
doi: 10.1007/s00432-007-0312-z. Epub 2007 Sep 25.

Identification and expression analysis of novel LAGE-1 alleles with single nucleotide polymorphisms in cancer patients

Yi Shao  1 , Zhen-Yuan Sun, Shi-Wei Sun, Yi Zhao, Wan Yee Sin, Yan-Hua Yuan, Andrew J Simpson, Lloyd J Old, Xin-Ting Sang, Yi-Lei Mao, Yong Xie, Jie-Fu Huang, Hai-Tao Zhao
Affiliations

Identification and expression analysis of novel LAGE-1 alleles with single nucleotide polymorphisms in cancer patients

Yi Shao et al. J Cancer Res Clin Oncol. 2008 Apr.

Abstract

Objective: 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.

Methods: In this study, different mRNAs transcribed from the LAGE-1 gene were identified by RT-PCR from healthy donors and cancer patients samples.

Results: 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.

Conclusion: 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.

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Figures

Fig. 1
Fig. 1
Alignment of the three LAGE-1a (A), LAGE-1b (B), and NY-ESO-1 (C) transcripts (CLUSTAL W (1.82)). Single nucleotide polymorphism sites are marked in bold and underscored. The underscored ATG and TAA are the start and stop codons for protein translation
Fig. 1
Fig. 1
Alignment of the three LAGE-1a (A), LAGE-1b (B), and NY-ESO-1 (C) transcripts (CLUSTAL W (1.82)). Single nucleotide polymorphism sites are marked in bold and underscored. The underscored ATG and TAA are the start and stop codons for protein translation
Fig. 2
Fig. 2
Three SNPs were identified in LAGE-1 gene by direct sequencing of PCR products from both PBMC and tumor derived DNA. SNP sites are indicated by red arrows. a SNP1, 1. Nucleotide A was detected in most of the population; 2. G and A were detected in a female donor. b SNP2, 1. Nucleic acid C was detected in most of the population; 2. G and C were detected in the same female donor as above. c SNP3, Column 1. Nucleic acid T was detected in most of the population; Column 2. G and T were detected in the same female donor as above
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