A haplotype of TGFBR1 is predominantly found in non-small cell lung cancer patients displaying TGFBR1 allelic-specific expression.

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.