Chromosome missegregation leads to chromosomal instability (CIN), thought to play a role in cancer development. As cohesin functions in guaranteeing correct chromosome segregation, increasing data suggest its involvement in tumorigenesis. In a screen of a large series of early colorectal adenomas, a precocious step during colorectal tumorigenesis, we identified 11 mutations in SMC1A core cohesin subunit. In addition, we sequenced the SMC1A gene in colorectal carcinomas and we found only one mutation. Finally, the transfection of the SMC1A mutations identified in early adenomas and wild-type SMC1A gene silencing in normal human fibroblasts led to CIN. Our findings that SMC1A mutations decrease from early adenomas to colorectal cancers and that mutations lead to CIN suggest that mutant cohesin could play a pivotal role during colorectal cancer development.

Mutant cohesin drives chromosomal instability in early colorectal adenomas / Cucco, F; Servadio, A; Gatti, V; Bianchi, P; Mannini, L; Prodosmo, A; De Vitis, E; Basso, G; Friuli, A; Laghi, L; Soddu, S; Fontanini, G; Musio, A. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - 23:25(2014), pp. 6773-6778. [10.1093/hmg/ddu394]

Mutant cohesin drives chromosomal instability in early colorectal adenomas

Laghi L;
2014-01-01

Abstract

Chromosome missegregation leads to chromosomal instability (CIN), thought to play a role in cancer development. As cohesin functions in guaranteeing correct chromosome segregation, increasing data suggest its involvement in tumorigenesis. In a screen of a large series of early colorectal adenomas, a precocious step during colorectal tumorigenesis, we identified 11 mutations in SMC1A core cohesin subunit. In addition, we sequenced the SMC1A gene in colorectal carcinomas and we found only one mutation. Finally, the transfection of the SMC1A mutations identified in early adenomas and wild-type SMC1A gene silencing in normal human fibroblasts led to CIN. Our findings that SMC1A mutations decrease from early adenomas to colorectal cancers and that mutations lead to CIN suggest that mutant cohesin could play a pivotal role during colorectal cancer development.
2014
Mutant cohesin drives chromosomal instability in early colorectal adenomas / Cucco, F; Servadio, A; Gatti, V; Bianchi, P; Mannini, L; Prodosmo, A; De Vitis, E; Basso, G; Friuli, A; Laghi, L; Soddu, S; Fontanini, G; Musio, A. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - 23:25(2014), pp. 6773-6778. [10.1093/hmg/ddu394]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2876790
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