Format

Send to

Choose Destination
Hum Mol Genet. 2014 Dec 20;23(25):6773-8. doi: 10.1093/hmg/ddu394. Epub 2014 Jul 30.

Mutant cohesin drives chromosomal instability in early colorectal adenomas.

Author information

1
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy Dipartimento di Biologia, Università degli Studi di Pisa, Pisa, Italy.
2
Dipartimento di Patologia Chirurgica, Medica, Molecolare e di Area Critica, Università di Pisa, Pisa, Italy.
3
Oncologia Sperimentale, Istituto Nazionale Tumori Regina Elena, Roma, Italy.
4
Humanitas Clinical and Research Center, Rozzano (MI), Italy and.
5
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy.
6
Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy Istituto Toscano Tumori, Firenze, Italy antonio.musio@irgb.cnr.it.

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.

PMID:
25080505
DOI:
10.1093/hmg/ddu394
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center