MDSC 515 EXAM SCRIPT 2025/2026 QUESTIONS AND
SOLUTIONS GRADED A+ TIP
✔✔types of targeted therapies - ✔✔-receptor tyrosine kinase pathway targets are the
most common
-monoclonal antibodies target the receptors upstream
-small molecule inhibitors such as tyrosine kinase inhibitors are used more downstream
✔✔somatic mutations - ✔✔-non-germline tissue
-non-heritable (acquired)
-involved in disease development
-need to test the tumour or any cells that come from the diseased organ as the mutation
will not be present anywhere else
✔✔germ-line mutations - ✔✔-present in egg or sperm
-heritable
-cause cancer family syndrome (inherited)
-in every tissue affected - can test skin, blood, tissues, affected as found in all of the
cells
✔✔tumour testing and multi-hit hypothesis - ✔✔-tumours have variable mutation profiles
and multiple different mutations
-specific mutations may or may not be relevant
-different types of mutations are relevant to specific genes
-focus molecular analysis on oncogenes and tumour suppressors
✔✔stepwise progression model of cancer - ✔✔-clonality: condition of being genetically
identical yo a parent, sibling, or other biological source
-cancer arises from clonal evolution of genetically abnormal cells - clonal evolution
causes mutations to accumulate and therefore there is an increasing amount of change
from the normal cell
-multiple mutations required through a process for it to manifest as cancer
✔✔multi-hit hypothesis - ✔✔-cancer does not arise from a single genetic event
-multiple mutations and epigenetic changes are required to promote carcinogenesis and
mainly occurs through oncogenes and tumour suppressors (driver genes of cancer)
✔✔oncogenes - ✔✔-predispose to cancer formation
-involved in cell growth, proliferation or inhibition of apoptosis
-over-expression or inappropriately activated in cancer cells
-often dominant mutations - only one mutation required to cause the effect
-often involved in the mitogenic pathway
-good therapeutic targets because they can be inhibited
-also redundant so if you block one path another can arise in its place
,✔✔typical alterations of oncogenes - ✔✔-activating point mutations
-copy number amplification
-translocations and fusions
✔✔tumor suppressor genes - ✔✔-genes that act to protect cells from becoming
cancerous
-involved in inhibition of growth, promotion of apoptosis or repair of DNA damage
-typically recessive and two hits are needed to see loss of function
-most inherited cancer syndromes arise from inheritance of a single hit in a tumour
suppressor - requires one more hit to this cell for cancer development
✔✔double mutation - ✔✔-two different inactivations to destroy gene
✔✔loss of heterozygosity - ✔✔-mutation in one copy of the gene and then the tumour
deletes the other copy or it is lost due to chromosome instability
✔✔types of alternations to tumour suppressors - ✔✔-frameshift mutations
-in/dels (lead to frame shift)
-copy number changes - whole gene deletions
✔✔Single nucleotide variants - ✔✔-mutation that changes one base (reference) for
another (variant)
✔✔transition mutation - ✔✔SNV that changes purine to purine or a pyrimidine to a
pyrimidine (A or G to C or T)
✔✔Transversion mutation - ✔✔SNV that changes purine to pyrimidine or a pyrimidine to
a purine (A to T or C)
✔✔synonymous mutation - ✔✔-SNV that does not change the coded amino acid
✔✔missense mutation - ✔✔SNV that causes a change in the coded amino acid
✔✔nonsense/stopgain mutation - ✔✔-SNV that introduces a stop codon
✔✔stopless mutation - ✔✔SNV that removes a stop codon
✔✔Single nucleotide polymorphism - ✔✔-not the same as SNV/point mutations
-a variant from the accepted gene sequence that exists in the general population at
>1.5% - random genetic diversity
-can be associated with increased risk of disease or may just be normal variation
✔✔in/dels - ✔✔-insertion or deletion of 1-50bp of DNA
, -unless in a multiple of 3 - indels produce frameshift - usually results in loss of function -
in frame indels may result in loss of function or gain of function
✔✔consequences of in/dels - ✔✔-usually result in protein truncation and reduced
function - cause a stop codon to be produced earlier than normal
✔✔exon skipping - ✔✔mutations in the donor/acceptor sequences or loop sequence
results in abnormal splice variants
-mutations can cause the alteration of the coding region/start site and therefore some
exons may be spliced out in the loop
✔✔splicing - RNA processing - ✔✔-post transcription processing to remove introns from
the primary RNA to form the messenger RNA
-intron gets spliced out and exons are included
✔✔Met kinase and exon skipping - ✔✔-MET is a receptor tyrosine kinase containing
regulatory exon 14 that controls protein stability
-exon skipping mutations in lung cancer remove exon 14 - MET is no longer regulated
-MET is over expressed and acts as an oncogene (proliferation)
✔✔Consequences of translocations - ✔✔-break large intronic regions
-fusion mRNA can be formed that forms an abnormal protein if transaction places part
of one gene next to another then fusion can occur during transcription
-there could also be a promoter-gene fusion causing altered expression
✔✔differences between RNA and DNA - ✔✔-single stranded vs double stranded
-no introns
-uracil replaces thymine
-additional 2' hydroxyl group on ribose sugar
✔✔pros of analyzing DNA - ✔✔-stable, abundant
-equal numbers of all genes (2 per cell)
-intrinsic copy number controls
-somatic and inherited mutations are easy to test for
-antisense strand confirmation of mutations
-easier to get from tissue
✔✔cons of analyzing DNA - ✔✔-intronic distance limits gene fusion detection by PCR
-no expression information (geno=pheno correlation)
-pseudogene amplification
✔✔pros of analyzing DNA - ✔✔-more direct gene-pheno correlation - can use levels to
see if they respond to therapy - proteins are linked to phenotype
-lack of introns facilitates fusion gene detection
-expression level analysis - if RNA expressed then protein expressed
SOLUTIONS GRADED A+ TIP
✔✔types of targeted therapies - ✔✔-receptor tyrosine kinase pathway targets are the
most common
-monoclonal antibodies target the receptors upstream
-small molecule inhibitors such as tyrosine kinase inhibitors are used more downstream
✔✔somatic mutations - ✔✔-non-germline tissue
-non-heritable (acquired)
-involved in disease development
-need to test the tumour or any cells that come from the diseased organ as the mutation
will not be present anywhere else
✔✔germ-line mutations - ✔✔-present in egg or sperm
-heritable
-cause cancer family syndrome (inherited)
-in every tissue affected - can test skin, blood, tissues, affected as found in all of the
cells
✔✔tumour testing and multi-hit hypothesis - ✔✔-tumours have variable mutation profiles
and multiple different mutations
-specific mutations may or may not be relevant
-different types of mutations are relevant to specific genes
-focus molecular analysis on oncogenes and tumour suppressors
✔✔stepwise progression model of cancer - ✔✔-clonality: condition of being genetically
identical yo a parent, sibling, or other biological source
-cancer arises from clonal evolution of genetically abnormal cells - clonal evolution
causes mutations to accumulate and therefore there is an increasing amount of change
from the normal cell
-multiple mutations required through a process for it to manifest as cancer
✔✔multi-hit hypothesis - ✔✔-cancer does not arise from a single genetic event
-multiple mutations and epigenetic changes are required to promote carcinogenesis and
mainly occurs through oncogenes and tumour suppressors (driver genes of cancer)
✔✔oncogenes - ✔✔-predispose to cancer formation
-involved in cell growth, proliferation or inhibition of apoptosis
-over-expression or inappropriately activated in cancer cells
-often dominant mutations - only one mutation required to cause the effect
-often involved in the mitogenic pathway
-good therapeutic targets because they can be inhibited
-also redundant so if you block one path another can arise in its place
,✔✔typical alterations of oncogenes - ✔✔-activating point mutations
-copy number amplification
-translocations and fusions
✔✔tumor suppressor genes - ✔✔-genes that act to protect cells from becoming
cancerous
-involved in inhibition of growth, promotion of apoptosis or repair of DNA damage
-typically recessive and two hits are needed to see loss of function
-most inherited cancer syndromes arise from inheritance of a single hit in a tumour
suppressor - requires one more hit to this cell for cancer development
✔✔double mutation - ✔✔-two different inactivations to destroy gene
✔✔loss of heterozygosity - ✔✔-mutation in one copy of the gene and then the tumour
deletes the other copy or it is lost due to chromosome instability
✔✔types of alternations to tumour suppressors - ✔✔-frameshift mutations
-in/dels (lead to frame shift)
-copy number changes - whole gene deletions
✔✔Single nucleotide variants - ✔✔-mutation that changes one base (reference) for
another (variant)
✔✔transition mutation - ✔✔SNV that changes purine to purine or a pyrimidine to a
pyrimidine (A or G to C or T)
✔✔Transversion mutation - ✔✔SNV that changes purine to pyrimidine or a pyrimidine to
a purine (A to T or C)
✔✔synonymous mutation - ✔✔-SNV that does not change the coded amino acid
✔✔missense mutation - ✔✔SNV that causes a change in the coded amino acid
✔✔nonsense/stopgain mutation - ✔✔-SNV that introduces a stop codon
✔✔stopless mutation - ✔✔SNV that removes a stop codon
✔✔Single nucleotide polymorphism - ✔✔-not the same as SNV/point mutations
-a variant from the accepted gene sequence that exists in the general population at
>1.5% - random genetic diversity
-can be associated with increased risk of disease or may just be normal variation
✔✔in/dels - ✔✔-insertion or deletion of 1-50bp of DNA
, -unless in a multiple of 3 - indels produce frameshift - usually results in loss of function -
in frame indels may result in loss of function or gain of function
✔✔consequences of in/dels - ✔✔-usually result in protein truncation and reduced
function - cause a stop codon to be produced earlier than normal
✔✔exon skipping - ✔✔mutations in the donor/acceptor sequences or loop sequence
results in abnormal splice variants
-mutations can cause the alteration of the coding region/start site and therefore some
exons may be spliced out in the loop
✔✔splicing - RNA processing - ✔✔-post transcription processing to remove introns from
the primary RNA to form the messenger RNA
-intron gets spliced out and exons are included
✔✔Met kinase and exon skipping - ✔✔-MET is a receptor tyrosine kinase containing
regulatory exon 14 that controls protein stability
-exon skipping mutations in lung cancer remove exon 14 - MET is no longer regulated
-MET is over expressed and acts as an oncogene (proliferation)
✔✔Consequences of translocations - ✔✔-break large intronic regions
-fusion mRNA can be formed that forms an abnormal protein if transaction places part
of one gene next to another then fusion can occur during transcription
-there could also be a promoter-gene fusion causing altered expression
✔✔differences between RNA and DNA - ✔✔-single stranded vs double stranded
-no introns
-uracil replaces thymine
-additional 2' hydroxyl group on ribose sugar
✔✔pros of analyzing DNA - ✔✔-stable, abundant
-equal numbers of all genes (2 per cell)
-intrinsic copy number controls
-somatic and inherited mutations are easy to test for
-antisense strand confirmation of mutations
-easier to get from tissue
✔✔cons of analyzing DNA - ✔✔-intronic distance limits gene fusion detection by PCR
-no expression information (geno=pheno correlation)
-pseudogene amplification
✔✔pros of analyzing DNA - ✔✔-more direct gene-pheno correlation - can use levels to
see if they respond to therapy - proteins are linked to phenotype
-lack of introns facilitates fusion gene detection
-expression level analysis - if RNA expressed then protein expressed
