• Cornelia de Lange syndrome
• Cohesin
• Colorectal cancer

Cohesin has a leading role in a wide range of chromosome-related processes. Its importance in cell biology is highlighted by the observation that cohesin alterations are causative for congenital human disorders and, as recently reported, could have a critical role in the development of many type of cancers. This PhD research was aimed in investigating the genetic effects of cohesin dysfunction with particular emphasis to CdLS and CRC. CdLS is genetic heterogeneous and 30% of patients lack of mutations in known genes. During the first part of this research project we planned to identify the additional causative CdLS gene(s) by WES analysis and, in parallel, to collect all of the identified CdLS mutations in order to define properly genotype-phenotype correlations. Most of sporadic CRC are characterized by CIN that arise since the early step of carcinogenesis. Mutations in cohesin complex has been found in colorectal carcinomas though at low frequencies. Because of the importance of cohesin in genome stability maintenance and preventing aneuploidy, our hypothesis was that cohesin mutations may occur in the early step of colorectal tumorigenesis and could be the crucial event in the development of CIN that characterize this type of cancer. In particular we focused on the study of SMC1A protein, not only because is one of the most conserved subunit, but also because it is directly involved in DNA damage response. To test this hypothesis we performed the mutational screening of SMC1A in colorectal adenomas, a precocious step of colorectal carcinogenesis. In addition, we investigated the effects on genome stability of cohesin mutations identified in colorectal adenomas.