Deletion and down-regulation of SMAD4 gene in colorectal cancers in a Chinese population

Chin J Cancer Res. 2014 Oct;26(5):525-31. doi: 10.3978/j.issn.1000-9604.2014.09.02.

Abstract

Objective: Colorectal cancer (CRC) is one of the most common types of human cancers. As a tumor suppressor, SMAD4 plays a key role in colorectal carcinogenesis and invasiveness. Copy number variations (CNVs) of the SMAD4 gene have been reported to be associated with cancer pathogenesis in array-based studies in different populations. Here we aimed to investigate the CNVs of the SMAD4 gene in a relatively large number of CRC patients from China.

Methods: In the present study, we collected 147 Chinese CRC tumors as well as self-paired normal control tissues. Quantitative PCR was carried out to examine the copy number as well as the mRNA expression of the SMAD4 gene.

Results: Our results showed that the copy number deletions of SMAD4 were frequent in a relatively high percentage of CRC samples (34.7%, 51 out of 147). There was a positive correlation between the copy number decrease of SMAD4 and tumor progression in CRCs. Furthermore, copy number loss of SMAD4 was correlated with decreased mRNA expression.

Conclusions: These findings suggested that the copy number deletions of SMAD4 were frequent in CRC patients from China and had the potential to serve as a diagnostic indicator, alone or in combination with other markers, for CRC.

Keywords: Colorectal cancer (CRC); SMAD4; copy number variation (CNV); gene expression.