2014
DOI: 10.1093/hmg/ddu394
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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, … Show more

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Cited by 32 publications
(32 citation statements)
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“…Cohesin, best known for its function in chromosome segregation, has been found to play a role in cancer progression (48). Sequencing of cancer genomes has also revealed the presence of somatic mutations in cohesin in various cancers.…”
Section: Cin In Precursor Lesionsmentioning
confidence: 99%
“…Cohesin, best known for its function in chromosome segregation, has been found to play a role in cancer progression (48). Sequencing of cancer genomes has also revealed the presence of somatic mutations in cohesin in various cancers.…”
Section: Cin In Precursor Lesionsmentioning
confidence: 99%
“…Indeed, Boveri proposed that chromosomal instability (CIN), resulting from whole or partial chromosomal gains and losses, was a critical event in tumorigenesis more than a century ago (Boveri and Boveri 1929). CIN may occur relatively early based on its prevalence in premalignancy (Rabinovitch et al 1989;Heaphy et al 2009;Cucco et al 2014). For example, genomic instability was shown to increase in atypical ductal hyperplasia (ADH) relative to normal tissue but to plateau in DCIS to invasive disease, suggesting that invasive carcinomas evolve from or in parallel to DCIS (Heaphy et al 2009).…”
Section: Big Bang Tumor Growth and Clonal Evolutionmentioning
confidence: 99%
“…In particular, alterations of genes belonging to the cohesin network have been reported in several types of cancer [Mannini et al, ; Mannini and Musio, ; Losada, ]. Moreover, mutations in cohesin factors have been associated with specific tumor stages and grades [Cucco et al, ; Taylor et al, ]. Interestingly, a recent report showed that genomic cohesin‐binding sites are frequently mutated in colorectal cancer samples [Katainen et al, ], corroborating the key role of cohesin dysfunctions in cancer development and progression.…”
Section: Resultsmentioning
confidence: 88%
“…In addition, in recent years mutations in core cohesin genes and auxiliary factors have been associated with carcinogenesis (Table , Fig. ) [Barber et al, ; Solomon et al, ; Welch et al, ; Balbas‐Martinez et al, ; Kon et al, ; Brohl et al, ; Cucco et al, ; Viny et al, ]. GIN is a well‐established hallmark of cancer cell phenotypes and for some cancers, such as colorectal carcinoma, it is predictive of a poor prognosis [Carter et al, ].…”
Section: Cohesin: One Ring To Rule Them Allmentioning
confidence: 99%
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