Describe how the development of colorectal cancer can be as a form of Darwinian Evolution.
Darwinian Evolution describes the process by which organisms that are better suited to the
environment tend to become more prevalent in a population over time. Darwinian Evolution can be
observed in the progression of colorectal cancer as Tumorigenesis itself begins when a particular
mutation in a normal cell allows it to overcome growth restraints which typically allow tissue
homeostasis. Having overcome these restraints, it can ‘outcompete’ surrounding cells and thus
continue to divide at an increasingly faster rate compared to its competitors and achieve limitless
replicative potential. How did Darwin come up with his theory of evolution? Darwin observed that
differences in physical characteristics of finches on the Galapagos Island such as their beak shape
and size were suited to their own unique surroundings.
Darwin observed variation amongst members of a species. Although later discovered, genetic
mutation was found to be the source of variation amongst a species.
It is estimated that 4-5 mutations are required for a normal cell to transform into a malignant cell
the evolution of colorectal cancer occurs in stages as described by the. Clonal expansion occurs
when a particular cell with a particular set of mutations that results in ‘peak fitness’ and this results
in linear evolution or a clonal sweep as this particular clone outcompetes all other competitors.
Truncal Mutations are mutations that are present in every clone in the tumour. These are inevitably
sourced from the dominant clone initiating the most recent clonal sweep at any point in time during
the progression of the tumour. Increased Branching of cell lineages occurs with microsatellite
instability. How are passenger mutations and oncodriver mutations differentiated ? We can compare
the mutational profiles of both normal and tumour cells though use of PCR.
Selection of cells based on their evolutionary viability can be divided into three types – positive
selection, neutral selection and negative selection. Positive Selection can promote resistance to
chemotherapy amongst tumours. For example, KRAS mutation confers resistance to Anti EGFR
Therapy such as cexitumab amongst metastatic colorectal cancer patients. Thus, cells with a KRAS
mutation within the tumour are ‘selected’ for and those that are not against. Neutral Selection
occurs when a mutation does not offer any selective advantage nor disadvantage. While less
common, negative selection occurs when a mutation offers a selective disadvantage to tumour
growth.
What is punctual evolution? is an evolutionary model which describes the progression of a tumour
as through stages of little activity and periods of rapid growth. In regard to a tumour, periods of little
evolutionary growth are characterized through neutral selection. If a mutation does not provide any
evolutionary benefit it will neither be selected for or against. These mutations are passenger
mutations.
It is estimated that 4-5 mutations are required for a normal cell to transform into a malignant cell
Development of colorectal cancer or the adenoma- carcinoma sequence was first accurately
described by the Feron Volgenstein model. The histological progression of colorectal cancer closely
follows this sequence of mutations.
APC > KRAS > q19 >p53.
APC acts as a tumour suppressor, by regulating a multitude of genes related to the cell cycle. A
mutant KRAS allele codes for an overacting GTPase with increased affinity for GTP. Q19 is then
mutated and finally pp53. This sequence of mutations seems to be crucial and both conserved
amongst all different cases of colorectal cancer. Despite chemotherapy a certain number of cells will
Darwinian Evolution describes the process by which organisms that are better suited to the
environment tend to become more prevalent in a population over time. Darwinian Evolution can be
observed in the progression of colorectal cancer as Tumorigenesis itself begins when a particular
mutation in a normal cell allows it to overcome growth restraints which typically allow tissue
homeostasis. Having overcome these restraints, it can ‘outcompete’ surrounding cells and thus
continue to divide at an increasingly faster rate compared to its competitors and achieve limitless
replicative potential. How did Darwin come up with his theory of evolution? Darwin observed that
differences in physical characteristics of finches on the Galapagos Island such as their beak shape
and size were suited to their own unique surroundings.
Darwin observed variation amongst members of a species. Although later discovered, genetic
mutation was found to be the source of variation amongst a species.
It is estimated that 4-5 mutations are required for a normal cell to transform into a malignant cell
the evolution of colorectal cancer occurs in stages as described by the. Clonal expansion occurs
when a particular cell with a particular set of mutations that results in ‘peak fitness’ and this results
in linear evolution or a clonal sweep as this particular clone outcompetes all other competitors.
Truncal Mutations are mutations that are present in every clone in the tumour. These are inevitably
sourced from the dominant clone initiating the most recent clonal sweep at any point in time during
the progression of the tumour. Increased Branching of cell lineages occurs with microsatellite
instability. How are passenger mutations and oncodriver mutations differentiated ? We can compare
the mutational profiles of both normal and tumour cells though use of PCR.
Selection of cells based on their evolutionary viability can be divided into three types – positive
selection, neutral selection and negative selection. Positive Selection can promote resistance to
chemotherapy amongst tumours. For example, KRAS mutation confers resistance to Anti EGFR
Therapy such as cexitumab amongst metastatic colorectal cancer patients. Thus, cells with a KRAS
mutation within the tumour are ‘selected’ for and those that are not against. Neutral Selection
occurs when a mutation does not offer any selective advantage nor disadvantage. While less
common, negative selection occurs when a mutation offers a selective disadvantage to tumour
growth.
What is punctual evolution? is an evolutionary model which describes the progression of a tumour
as through stages of little activity and periods of rapid growth. In regard to a tumour, periods of little
evolutionary growth are characterized through neutral selection. If a mutation does not provide any
evolutionary benefit it will neither be selected for or against. These mutations are passenger
mutations.
It is estimated that 4-5 mutations are required for a normal cell to transform into a malignant cell
Development of colorectal cancer or the adenoma- carcinoma sequence was first accurately
described by the Feron Volgenstein model. The histological progression of colorectal cancer closely
follows this sequence of mutations.
APC > KRAS > q19 >p53.
APC acts as a tumour suppressor, by regulating a multitude of genes related to the cell cycle. A
mutant KRAS allele codes for an overacting GTPase with increased affinity for GTP. Q19 is then
mutated and finally pp53. This sequence of mutations seems to be crucial and both conserved
amongst all different cases of colorectal cancer. Despite chemotherapy a certain number of cells will
