Disputation and trial lecture
Kristine Kleivi
Kristine Kleivi
She gave her trial lecture for her doctoral thesis on March 23rd, on the subject "How can altered regulation of chromatin formation lead to congenital genetic disease?"
Both events took place in the Auditorium at the Norwegian Radium Hospital.
Links:
Read the announcement from UiO's web pages (in Norwegian).
The thesis originates from the Molecular Cancer Genetics group led by Ragnhild A. Lothe at the Department of Genetics at The Norwegian Institute for Cancer Research.
Supervisor: Ragnhild A. Lothe
Kristine Kleivi
Current position: Post Doc at VTT Technical Research Centre of Finland, Turku, Finland.
SUMMARY:
Colorectal cancer is one of the most common malignancies in the Western world, and half of the patients who develop this disease die within five years. The disease develops through different histopathological steps, followed by an accumulation of genetic and epigenetic changes. A subgroup of twelve to fifteen percent of all primary colorectal carcinomas is typically near-diploid, but display genome wide microsatellite instability. However, the majority of colorectal carcinomas harbour numerous aberrations at the chromosome level, and chromosomal instability seems to be pronounced in these tumours.
This thesis identifies and evaluates the genetic and epigenetic changes in colorectal cancers at the global genome- and transcriptome level as well as for single genes. The genomic changes in a series of colorectal cancer cell lines are identified, and different profiles characterise the two pathways of instability, microsatellite- and chromosomal instability. Details in genome characterisation are important as these cancer cell lines are used extensively as controls and models in cancer research. By treating the cell lines with a drug that removes methylation followed by microarray analyses, three genes are identified as novel epigenetic targets by transcriptional silencing in the colorectal tumourigenesis.
Despite the fact that metastases are the leading cause of colorectal cancer death, the molecular mechanisms involved in the metastatic process of CRC remain mostly unknown. By performing a meta-analysis on CGH data, a genetic pathway for colorectal cancer progression from Dukes' A to Dukes' D and to liver metastases is suggested. Gene
expression profiles from different stages of the colorectal tumourigenesis reveal interesting candidate genes that might be important in colorectal cancer progression, and a gene pattern specific for spreading to the peritoneum from colorectal carcinomas are identified.
In the present thesis, new knowledge of the molecular biology related to colorectal cancer progression is presented by combining the use of relevant in vitro models with solid tumours.
This thesis identifies and evaluates the genetic and epigenetic changes in colorectal cancers at the global genome- and transcriptome level as well as for single genes. The genomic changes in a series of colorectal cancer cell lines are identified, and different profiles characterise the two pathways of instability, microsatellite- and chromosomal instability. Details in genome characterisation are important as these cancer cell lines are used extensively as controls and models in cancer research. By treating the cell lines with a drug that removes methylation followed by microarray analyses, three genes are identified as novel epigenetic targets by transcriptional silencing in the colorectal tumourigenesis.
Despite the fact that metastases are the leading cause of colorectal cancer death, the molecular mechanisms involved in the metastatic process of CRC remain mostly unknown. By performing a meta-analysis on CGH data, a genetic pathway for colorectal cancer progression from Dukes' A to Dukes' D and to liver metastases is suggested. Gene
expression profiles from different stages of the colorectal tumourigenesis reveal interesting candidate genes that might be important in colorectal cancer progression, and a gene pattern specific for spreading to the peritoneum from colorectal carcinomas are identified.
In the present thesis, new knowledge of the molecular biology related to colorectal cancer progression is presented by combining the use of relevant in vitro models with solid tumours.
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