Possible influences on the difference in mutation rates between CIN and MIN colorectal cancers

Jong, S.E.K. de (2017) Possible influences on the difference in mutation rates between CIN and MIN colorectal cancers. Bachelor's Thesis, Biology.

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Abstract

Colorectal cancer (CRC) is the fourth most common cancer type of cancer diagnosed in the western world. Genetic instability is a relevant source for both genetic and phenotypic diversity in this cancer. Oncogenes and tumour suppressor genes are often mutated and result in increased mutation rates which in turn, result in carcinogenesis. This genomic instability occurs through several pathways, in which two are discussed in this paper. One type of CRC results from chromosomal instability (CIN), which is due to the miss-segregation of chromosomes during mitosis, known as aneuploidy. CIN occurs in 85% of the colorectal cancers. The other 15% is due to microsatellite instability (MIN), which results from a defect in the mismatch repair system during cell division. These two mechanisms are widely studied and differences in phenotypes, mutations, prognoses and mutation rates have been analysed. However, studies in differences between progression rates are difficult to find, but could still be important for understanding certain CRC mechanisms. However, research has revealed extensive differences within MIN tumours and CIN tumours. For example, MIN mutation rates can increase with increase in microsatellite length, which has less association with CIN tumours. MIN CRC shows better prognosis than CIN CRC, which might be a result of a lower progression rate. In addition, MIN tumours tend to occur more frequently in earlier stages than CIN tumours, which are often seen in stage II and III colorectal cancer. The probability for a MIN-associated MMR defect is 0,01% per cell division, whereas the chance that a chromosome miss-segregates and therefore CIN occurs, is ~25%. This suggests that CIN occurs 250 times more frequently than MIN. Unfortunately, CRC is a very complex disease where differences arise between CIN and MIN tumours, heterogeneity, genes, tissues, stages and origins of the cancer. Therefore, this extreme diversity makes it a challenge to make specific comparisons between CIN and MIN, but not less important.

Item Type:	Thesis (Bachelor's Thesis)
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	15 Feb 2018 08:29
Last Modified:	15 Feb 2018 08:29
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/15307

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