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Deregulation of the replisome factor MCMBP prompts oncogenesis in colorectal carcinomas through chromosomal instability

(2014) NEOPLASIA. 16(9). p.694-709
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Abstract
Genetic instability has emerged as an important hallmark of human neoplasia. Although most types of cancers exhibit genetic instability to some extent, in colorectal cancers genetic instability is a distinctive characteristic. Recent studies have shown that deregulation of genes involved in sister chromatid cohesion can result in chromosomal instability in colorectal cancers. Here, we show that the replisome factor minichromosome maintenance complex-binding protein (MCMBP), which is directly involved in the dynamics of the minichromosome maintenance complex and contributes to maintaining sister chromatid cohesion, is transcriptionally misregulated in different types of carcinomas. Cellular studies revealed that both MCMBP knockdown and overexpression in different breast and colorectal cell lines is associated with the emergence of a subpopulation of cells with abnormal nuclear morphology that likely arise as a consequence of aberrant cohesion events. Association analysis integrating gene expression data with clinical information revealed that enhanced MCMBP transcript levels correlate with an increased probability of relapse risk in colorectal cancers and different types of carcinomas. Moreover, a detailed study of a cohort of colorectal tumors showed that the MCMBP protein accumulates to high levels in cancer cells, whereas in normal proliferating tissue its abundance is low, indicating that MCMBP could be exploited as a novel diagnostic marker for this type of carcinoma.
Keywords
KINASE 1, MAINTENANCE, DNA-REPLICATION, BREAST-CANCER, GENOMIC INSTABILITY, REPLICATION FORK, SISTER-CHROMATID COHESION, IDENTIFICATION, ANEUPLOIDY, COMPLEX

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Chicago
Quimbaya Gomez, Mauricio Alberto, Eric Raspé, Geertrui Denecker, Bram De Craene, Ria Roelandt, Wim Declercq, Xavier Sagaert, Lieven De Veylder, and Geert Berx. 2014. “Deregulation of the Replisome Factor MCMBP Prompts Oncogenesis in Colorectal Carcinomas Through Chromosomal Instability.” Neoplasia 16 (9): 694–709.
APA
Quimbaya Gomez, M. A., Raspé, E., Denecker, G., De Craene, B., Roelandt, R., Declercq, W., Sagaert, X., et al. (2014). Deregulation of the replisome factor MCMBP prompts oncogenesis in colorectal carcinomas through chromosomal instability. NEOPLASIA, 16(9), 694–709.
Vancouver
1.
Quimbaya Gomez MA, Raspé E, Denecker G, De Craene B, Roelandt R, Declercq W, et al. Deregulation of the replisome factor MCMBP prompts oncogenesis in colorectal carcinomas through chromosomal instability. NEOPLASIA. 2014;16(9):694–709.
MLA
Quimbaya Gomez, Mauricio Alberto, Eric Raspé, Geertrui Denecker, et al. “Deregulation of the Replisome Factor MCMBP Prompts Oncogenesis in Colorectal Carcinomas Through Chromosomal Instability.” NEOPLASIA 16.9 (2014): 694–709. Print.
@article{5732523,
  abstract     = {Genetic instability has emerged as an important hallmark of human neoplasia. Although most types of cancers exhibit genetic instability to some extent, in colorectal cancers genetic instability is a distinctive characteristic. Recent studies have shown that deregulation of genes involved in sister chromatid cohesion can result in chromosomal instability in colorectal cancers. Here, we show that the replisome factor minichromosome maintenance complex-binding protein (MCMBP), which is directly involved in the dynamics of the minichromosome maintenance complex and contributes to maintaining sister chromatid cohesion, is transcriptionally misregulated in different types of carcinomas. Cellular studies revealed that both MCMBP knockdown and overexpression in different breast and colorectal cell lines is associated with the emergence of a subpopulation of cells with abnormal nuclear morphology that likely arise as a consequence of aberrant cohesion events. Association analysis integrating gene expression data with clinical information revealed that enhanced MCMBP transcript levels correlate with an increased probability of relapse risk in colorectal cancers and different types of carcinomas. Moreover, a detailed study of a cohort of colorectal tumors showed that the MCMBP protein accumulates to high levels in cancer cells, whereas in normal proliferating tissue its abundance is low, indicating that MCMBP could be exploited as a novel diagnostic marker for this type of carcinoma.},
  author       = {Quimbaya Gomez, Mauricio Alberto and Rasp{\'e}, Eric and Denecker, Geertrui and De Craene, Bram and Roelandt, Ria and Declercq, Wim and Sagaert, Xavier and De Veylder, Lieven and Berx, Geert},
  issn         = {1522-8002},
  journal      = {NEOPLASIA},
  keyword      = {KINASE 1,MAINTENANCE,DNA-REPLICATION,BREAST-CANCER,GENOMIC INSTABILITY,REPLICATION FORK,SISTER-CHROMATID COHESION,IDENTIFICATION,ANEUPLOIDY,COMPLEX},
  language     = {eng},
  number       = {9},
  pages        = {694--709},
  title        = {Deregulation of the replisome factor MCMBP prompts oncogenesis in colorectal carcinomas through chromosomal instability},
  url          = {http://dx.doi.org/10.1016/j.neo.2014.07.011},
  volume       = {16},
  year         = {2014},
}

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