Micro-RNA copy number abnormalities in familial colorectal cancer

Abstract

The majority of the familial colorectal cancer (CRC) cases cannot be explained by known gene defects, suggesting the existence of other genetic risk factors. In an approach to identify such risk factors, we recently performed a screen for copy number variations (CNVs) in high-risk CRC patients and found, among other lesions, several small deletions affecting microRNA genes. MicroRNAs are negative regulators of approximately 30% of the genes in the human genome, including numerous tumor suppressor genes and oncogenes. In order to comprehensively investigate copy number variation in microRNA genes, and to reveal whether such variations may affect CRC predisposition, we screened for CNVs of microRNA genes in 52 unexplained familial early-onset CRC patients using a custom-made ultimate (tiling) resolution oligo array containing 695 miR genes. We found various small (0.1e5 kb) constitutional deletions and duplications affecting single microRNA genes. Several of these (PCR-validated) CNVs could be detected also in normal controls, whereas others appeared to be rare and were thus far only found in CRC patients. We conclude that CNVs in microRNA genes are more common than previously thought, and that some of them may be associated with CRC predisposition. NOVEL TRANSLOCATION VARIANT IN EWING SARCOMA INVOLVING THE NFATC2 GENE