title: Mutant cohesin drives chromosomal instability in early colorectal adenomas.
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.
authors: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy Dipartimento di Biologia, Università degli Studi di Pisa, Pisa, Italy.
authors: Francesco
authors: F
authors: Cucco
authors: Dipartimento di Patologia Chirurgica, Medica, Molecolare e di Area Critica, Università di Pisa, Pisa, Italy.
authors: Adele
authors: A
authors: Servadio
authors: Oncologia Sperimentale, Istituto Nazionale Tumori Regina Elena, Roma, Italy.
authors: Veronica
authors: V
authors: Gatti
authors: Humanitas Clinical and Research Center, Rozzano (MI), Italy and.
authors: Paolo
authors: P
authors: Bianchi
authors: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy.
authors: Linda
authors: L
authors: Mannini
authors: Oncologia Sperimentale, Istituto Nazionale Tumori Regina Elena, Roma, Italy.
authors: Andrea
authors: A
authors: Prodosmo
authors: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy.
authors: Elisa
authors: E
authors: De Vitis
authors: Humanitas Clinical and Research Center, Rozzano (MI), Italy and.
authors: Gianluca
authors: G
authors: Basso
authors: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy.
authors: Alessandro
authors: A
authors: Friuli
authors: Humanitas Clinical and Research Center, Rozzano (MI), Italy and.
authors: Luigi
authors: L
authors: Laghi
authors: Oncologia Sperimentale, Istituto Nazionale Tumori Regina Elena, Roma, Italy.
authors: Silvia
authors: S
authors: Soddu
authors: Dipartimento di Patologia Chirurgica, Medica, Molecolare e di Area Critica, Università di Pisa, Pisa, Italy.
authors: Gabriella
authors: G
authors: Fontanini
authors: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy Istituto Toscano Tumori, Firenze, Italy antonio.musio@irgb.cnr.it.
authors: Antonio
authors: A
authors: Musio
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000782:Aneuploidy; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007621:Karyotyping; D008297:Male; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D034741:RNA, Small Interfering; D000098550:Structural Maintenance of Chromosome Protein 1