Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Department of Thoraco-cardiac Surgery, The First Affiliated Hospital, Suzhou 215123, PR China.
Oncol Rep. 2011 Mar;25(3):685-91. doi: 10.3892/or.2011.1135. Epub 2011 Jan 10.
Non-small cell lung cancer (NSCLC) accounts for ~85% of all cases of lung cancer and TGF-ß refractoriness is very common in NSCLC cells. Constitutively decreased TGFBR1 expression, probably leading to TGF-ß resistance in tumors, is emerging as a novel tumor-predisposing phenotype. However, the precise genetic/epigenetic mechanisms underlying the role of TGFBR1 in NSCLC carcinogenesis are still largely unknown. In the present study, we performed the SNaPshot method to quantify allelic-specific expression (ASE) of two chosen SNPs that are located in the 3' untranslated region (3' UTR) of the TGFBR1 gene. We selected seven tagging SNPs (tSNPs) of TGFBR1 to assess the relationship between ASE of TGFBR1 and tSNP-reconstructed haplotypes in NSCLC tumors. ASE of TGFBR1 was detected in 21.1% of NSCLC tumors. One tagging SNP (rs7040869) of TGFBR1 in the 5' flanking region was found to be significantly associated with TGFBR1 ASE in NSCLC tumors (P=0.03). A 2-tSNP AT haplotype reconstructed with tSNP rs7040869 and rs4743325, in linkage disequilibrium with each other, was strongly associated with NSCLC cases displaying ASE (P=0.01). In conclusion, our results shed light on the high frequency of TGFBR1 ASE phenotype in NSCLC tumors, which is associated with the 2-tSNP haplotype of the TGFBR1 gene. Although this suggests an important role of the TGFBR1 locus in the etiology of NSCLC, additional studies at the germline level and in various ethnic populations are warranted.
非小细胞肺癌（NSCLC）占所有肺癌病例的~85%，而转化生长因子-β（TGF-β）耐药在 NSCLC 细胞中非常常见。TGFBR1 表达的组成性降低，可能导致肿瘤中的 TGF-β 耐药，这是一种新的肿瘤易患表型。然而，TGFBR1 在 NSCLC 发生中的作用的精确遗传/表观遗传机制在很大程度上仍然未知。在本研究中，我们使用 SNaPshot 方法来定量 TGFBR1 基因 3'非翻译区（3'UTR）中两个选定 SNP 的等位基因特异性表达（ASE）。我们选择了七个 TGFBR1 的标签 SNP（tSNP）来评估 TGFBR1 的 ASE 与 NSCLC 肿瘤中 tSNP 重建单倍型之间的关系。在 21.1%的 NSCLC 肿瘤中检测到 TGFBR1 的 ASE。TGFBR1 的一个标签 SNP（rs7040869）位于 5'侧翼区，与 NSCLC 肿瘤中的 TGFBR1 ASE 显著相关（P=0.03）。与 tSNP rs7040869 和 rs4743325 连锁不平衡的 TGFBR1 的 2-tSNP AT 单倍型与显示 ASE 的 NSCLC 病例强烈相关（P=0.01）。总之，我们的结果揭示了 TGFBR1 ASE 表型在 NSCLC 肿瘤中的高频率，这与 TGFBR1 基因的 2-tSNP 单倍型相关。尽管这表明 TGFBR1 基因座在 NSCLC 的病因学中具有重要作用，但需要在胚系水平和各种种族人群中进行更多的研究。
