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In contrast, UPF2 was not differentially expressed in either MSI or MSS CRCs compared to matching normal mucosa (P = 0.56 and 0.83, respectively; paired t-test) (Figure 2).

Using this approach, the number of cases in which UPF1 expression was higher in tumors compared to matching normal mucosa (N = 20/25) was significantly different than expected by chance (P = 0.009; chi-square test).

In addition, an independent series of 25 MSI and 31 MSS primary CRC samples were collected in the same conditions together with their matching normal mucosa and used to compare UPF1 and UPF2 expression in tumor and normal colonic tissues.

Such a putative oncogenic function of NMD in MSI carcinogenesis fits well with the fact that we also report here for the first time that UPF1 is significantly over-expressed in MSI CRCs compared to matching normal mucosa.

By measuring the levels of UPF1 and UPF2 mRNAs by real-time quantitative RT-PCR in another independent series of MSI primary CRCs for which we also obtained the samples corresponding to matching normal mucosa, we observed an approximately 7-fold over-expression of UPF1 in tumors (n = 25) compared to normal mucosa (P = 0.0015; paired t-test) (Figure 2).

LS vs. FAP-associated adenomas and matching normal mucosa showed comparable frequencies of hypermethylation.

In (A, C, and E), the ratios of the β-actin-normalized expression in the tumors relative to the matched normal mucosa were presented in base two logarithm (log2[T/N]).

The ratios of β-actin-normalized expression in the tumors relative to that of the matched normal mucosa were presented in base two logarithm (log2[T/N]).

About 60% of tumors showed PPARG over-expression and 5% of cases showed not significant differences between tumour tissues and the matched normal mucosa.

There was no statistically significant difference between matched normal mucosa and polyps derived from the same cases, or between colonic mucosa from HPS cases and controls (colonic mucosa from cases with normal endoscopic findings and no history of polyps).

Contrary to previous reports [40]; [14], [14] we found that, MGMT and MLH1 were unmethylated (Fig. S1) in both polyps and matched normal mucosa, while there was no significant difference in DNA methylation of IGF2, H19, and WIF1 (Fig. S1) between polyp and disease free tissue.