Intratumoral heterogeneity for inactivating frameshift mutation of CUX1 and SIRT1 genes in gastric and colorectal cancers.

Both <I>CUX1</I> and <I>SIRT1</I> are considered tumor suppressor genes (TSGs), but it is not known whether <I>CUX1</I> and <I>SIRT1</I> alterations are different between high microsatellite instability (MSI-H) and microsatellite stable MSI (MSS) cancers. We identified frameshift mutations of <I>CUX1</I> in 4 cases of colorectal cancer (CRC) and of <I>SIRT1</I> in 1 case of gastric cancer (GC) and 3 cases of CRC. All of them were found in GC or CRC with MSI-H (3.5% of MSI-H for each gene), but neither in GC nor CRC with MSS. In addition, we analyzed intratumoral heterogeneity (ITH) of the <I>CUX1</I> frameshift mutation and found that two CRCs (12.5%) harbored regional ITH of the frameshift mutation. Our data indicate that there exist frameshift mutations of <I>CUX1</I> and <I>SIRT1</I> genes as well as ITH of <I>CUX1</I> frameshift mutation in MSI-H cancers, which together might play a role in tumorigenesis of GC and CRC with MSI-H.