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Background  Transcript dosage imbalance may influence the transcriptome. To gain insight into the role of altered gene expression in hereditary colorectal polyposis predisposition, in the present study we analyzed absolute and allele-specific expression (ASE) of  adenomatous polyposis coli  ( APC ) and  mutY Homolog  ( MUTYH ) genes.    Methods  We analyzed DNA and RNA extracted from peripheral blood mononuclear cells (PBMC) of 49 familial polyposis patients and 42 healthy blood donors selected according similar gender and age. Patients were studied for germline alterations in both genes using dHPLC, MLPA and automated sequencing.  APC  and  MUTYH  mRNA expression levels were investigated by quantitative Real-Time PCR (qRT-PCR) analysis using TaqMan assay and by ASE assays using dHPLC-based primer extension.    Results  Twenty out of 49 patients showed germline mutations: 14 in  APC  gene and six in  MUTYH  gene. Twenty-nine patients did not show mutations in both genes. Results from qRT-PCR indicated that gene expression of both  APC  and  MUTYH  was reduced in patients analyzed. In particular, a significant reduction in  APC  expression was observed in patients without  APC  germline mutation  vs  control group ( P  < 0.05) while  APC  expression in the mutation carrier patients, although lower compared to control individuals, did not show statistical significance. On the other hand a significant reduced  MUTYH  expression was detected in patients with  MUTYH  mutations  vs  control group ( P  < 0.05). Altered ASE of  APC  was detected in four out of eight  APC  mutation carriers. In particular one case showed a complete loss of one allele. Among  APC  mutation negative cases, 4 out of 13 showed a moderate ASE. ASE of  MUTYH  did not show any altered expression in the cases analyzed. Spearman’s Rho Test analysis showed a positive and significant correlation between  APC  and  MUTYH  genes both in cases and in controls ( P  = 0.020 and  P  < 0.001).    Conclusions   APC  and  MUTYH  showed a reduced germline expression, not always corresponding to gene mutation. Expression of  APC  is decreased in mutation negative cases and this appears to be a promising indicator of FAP predisposition, while for  MUTYH  gene, mutation is associated to reduced mRNA expression. This study could improve the predictive genetic diagnosis of at-risk individuals belonging to families with reduced mRNA expression regardless of presence of mutation.    Electronic supplementary material  The online version of this article (doi:10.1186/s13046-015-0244-4) contains supplementary material, which is available to authorized users.

Correlation between mutations and mRNA expression of APC and MUTYH genes: new insight into hereditary colorectal polyposis predisposition