Mutations and Cancer

Question 1

methylation of promoter region of p53 tumour-suppressor gene

Answer 1

• RNA polymerase cannot bind at promoter region of p53 tsg
• p53 gene not transcribed and p53 not produced
• p53 tsg underexpressed compared to proto-oncogenes, so cell division not stopped even when cell contains damaged DNA
• uncontrolled cell division results
• result in malignant tumour formation in the individual person
• tumour interferes with normal functions of tissue via metastasis

Question 2

sickle-cell anaemia

Answer 2

• substitution of a single nucleotide, from CTT to CAT in the DNA’s template
• change in mRNA codon
• change in amino acid from glutamate to valine
• glu is hydrophilic while val is hydrophobic
• at low oxygen concentration, hydrophobic regions on different haemoglobin form hydrophobic interactions and stick together
• mutated haemoglobin tend to polymerise into long rigid chains when not bound to oxygen
• long fibres distort the membrane of rbc, giving it its sickle shape
• shape of rbc block the flow of blood, thus resulting in the decreased oxygen-carrying ability of the rbc

Question 3

cancer development is a multi-step process

Answer 3

• gain-of-function mutation in one copy of ras proto-oncogene and loss-of-function in two copies of p53 and APC tumour-suppressor gene
• accumulation of mutations in APC, p53 and ras results in uncontrolled cell division, forming malignant tumour, resulting in colon carcinoma
• invasion of cancer cells to surrounding tissues
• chromosomal abberation result in metastatic carcinoma, where cancer cells spread to distant sites can result in formation of secondary tumours

Question 4

how dysregulation of checkpoints of cell division may lead to cancer

Answer 4

• dysregulation of checkpoint at G1, G2 and M results in abnormal cell does not undergo apoptosis and continue with the cell cycle
• abnormal cell continues to divide and accumulate mutations resulting in uncontrolled cell division leading to malignant tumour formation
• if G1 checkpoint is dysregulated, there may be insufficient growth factors present for cell to undergo mitosis but the cell still proceeds to s phase
• if G2 checkpoint is dysregulated, there may be incomplete semi-conservative replication where some genes might be lost
• if M checkpoint is dysregulated, not all chromosomes may be attached to spindle fibres, resulting in aneuploid cells where there are additional genes

Question 5

role of tumour-suppressor genes

Answer 5

• tsg encode proteins that inhibit cell division
• loss-of-function mutation of tumour suppressor genes to mutated tsg leads to no protein product
• both alleles of tsg must be mutated for uncontrolled cell division to occur, hence, cancer to develop

Question 6

causative agent of cancer

Answer 6

• ultraviolet light : causes DNA to increase in energy level, causing the nitrogenous bases to be more reactive and react with surrounding molecules, leading to damage of DNA
• ethidium bromide : mutagens that cause chemical changes in bases resulting in incorrect base pairing, results in insertion or deletion of base pair

Question 7

gene mutation during replication of DNA

Answer 7

• DNA polymerase may make mistake during replication and proof-reading mechanisms did not detect mistake
• wrong nucleotide added to growing nucleotide chain, resulting in substitution mutation

Question 8

gain-of-function mutation vs loss-of-function mutation

Answer 8

• gof mutation occurs in proto-oncogene to form oncogene while lof mutation occurs in tumour-suppressor gene to form mutated tsg
• gof mutation results in increase amount in protein product synthesised/permanently activated proteins
• lof mutation results in no protein product/decrease in amount of protein product formed
• gof mutation results in a dominant allele while lof mutation results in a recessive allele
• only one allele needs to be mutated for gof mutation to take effect whereas both alleles need to be mutated for lof mutation to take effect

Question 9

types of structural chromosomal abberations

Answer 9

• deletion occurs when a chromosomal segment is lost and several genes may be missing
• duplication occurs when a chromosomal segment is repeated where detached chromosomal fragment from a sister chromatid become attached as an extra fragment to a non-sister chromatid of a homologous chromosome
• inversion occurs when a chromosomal segment breaks and reattaches to the original chromosome in a reverse orientation
• translocation occurs when a chromosomal fragment breaks and joins with a non-homologous chromosome

Question 10

missense mutation

Answer 10

• change in DNA sequence
• change in codon
• change in amino acid produced
• change in 3D conformation of protein
• change in protein’s function (more significant if substitution occurs in the active site of enzyme)

Question 11

nonsense mutation

Answer 11

• codon can be changed into a stop codon
• translation terminated prematurely
• polypeptide formed will be shorter than the polypeptide encoded by normal gene
• non-functional proteins produced

Question 12

frameshift mutation

Answer 12

• result of additional and deletional mutation
• reading frame is altered
• number of nucleotides inserted or deleted is not a multiple of three
• all the nucleotides that are downstream of the addition or deletion will be improperly grouped into codons
• extensive change in the sequence of amino acids
• premature termination
• non-functional protein produced

Question 13

types of gene mutation

Answer 13

• substitution is the replacement of one nucleotide pair with another pair of nucleotide
• addition is the insertion of one or more nucleotide pairs into a DNA sequence
• deletion is the removal of one or more nucleotide pairs from a DNA sequence