MDSC 515 EXAM STUDY GUIDE
biomarkers - Answers :-objective and quantifiable measurement or characteristic of a
biological process
-indicator of a biologic process
-molecular pathology = gene or gene product associated with a disease process
ideal biomarker - Answers :-relevant and valid to a specific disease state
-provides actionable or prognostic info
-quantifiable in easily obtained tissue or fluid
-economical to test in a reproducible fashion
caveat to biomarkers - Answers :-molecular pathology biomarkers can be the protein,
specific mutation, copy number alteration or the fusion gene product
-specific biomarker can be associated with multiple diseases and have multiple types of
alteration, each with different disease associations
types of biomarkers - Answers :-predisposition
-diagnostic
-prognostic
-predictive
predisposition biomarkers - Answers :-indicates a risk or likelihood that a disease
process will occur prior to symptoms
-prenatal screening for inherited syndromes
diagnostic biomarkers - Answers :-pathognomonic = defines/diagnoses the specific
entity - characteristic or indicative of disease
-typically the status of the biomarker is included in the diagnostic criteria for the disease
in question
-CFTR mutations are required for cystic fibrosis to develop
-some biomarkers are diagnostic of multiple diseases or some are diagnostic in one and
not another even if its present
prognostic biomarkers - Answers :-status of the biomarker provides info on how the
disease will behave independent of therapy (normal behaviour)
-example: patients with breast cancer that are negative for hormone receptors will have
worse outcomes than those that are positive for the receptors
predictive biomarkers - Answers :-status of the biomarker predicts/determines how the
disease will respond to different therapies
-if biomarker X is present, the disease will reliably respond positively or negatively to the
treatment Y
-mutations with targeted therapy (therapy will be beneficial or not to the disease)
,issues with therapies and treatments - Answers :-efficacy of therapies almost alway
derived from population data/stats
-a percent of the pop will not experience therapy benefit - therefore they are at risk for
therapy side effects
targeted therapy - Answers :-specific therapy that takes advantage of disease
associated biomarkers
-substratify the treatments for the same disease based on the biomarkers that an
individual possesses
-it is targeted because the biomarker is usually only associated with the disease and the
normal tissue is less affected
types of targeted therapies - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-activating point mutations
-copy number amplification
-translocations and fusions
tumor suppressor genes - Answers :-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 - Answers :-two different inactivations to destroy gene
loss of heterozygosity - Answers :-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 - Answers :-frameshift mutations
-in/dels (lead to frame shift)
-copy number changes - whole gene deletions
Single nucleotide variants - Answers :-mutation that changes one base (reference) for
another (variant)
transition mutation - Answers :SNV that changes purine to purine or a pyrimidine to a
pyrimidine (A or G to C or T)
Transversion mutation - Answers :SNV that changes purine to pyrimidine or a
pyrimidine to a purine (A to T or C)
synonymous mutation - Answers :-SNV that does not change the coded amino acid
missense mutation - Answers :SNV that causes a change in the coded amino acid
nonsense/stopgain mutation - Answers :-SNV that introduces a stop codon
stopless mutation - Answers :SNV that removes a stop codon
Single nucleotide polymorphism - Answers :-not the same as SNV/point mutations
biomarkers - Answers :-objective and quantifiable measurement or characteristic of a
biological process
-indicator of a biologic process
-molecular pathology = gene or gene product associated with a disease process
ideal biomarker - Answers :-relevant and valid to a specific disease state
-provides actionable or prognostic info
-quantifiable in easily obtained tissue or fluid
-economical to test in a reproducible fashion
caveat to biomarkers - Answers :-molecular pathology biomarkers can be the protein,
specific mutation, copy number alteration or the fusion gene product
-specific biomarker can be associated with multiple diseases and have multiple types of
alteration, each with different disease associations
types of biomarkers - Answers :-predisposition
-diagnostic
-prognostic
-predictive
predisposition biomarkers - Answers :-indicates a risk or likelihood that a disease
process will occur prior to symptoms
-prenatal screening for inherited syndromes
diagnostic biomarkers - Answers :-pathognomonic = defines/diagnoses the specific
entity - characteristic or indicative of disease
-typically the status of the biomarker is included in the diagnostic criteria for the disease
in question
-CFTR mutations are required for cystic fibrosis to develop
-some biomarkers are diagnostic of multiple diseases or some are diagnostic in one and
not another even if its present
prognostic biomarkers - Answers :-status of the biomarker provides info on how the
disease will behave independent of therapy (normal behaviour)
-example: patients with breast cancer that are negative for hormone receptors will have
worse outcomes than those that are positive for the receptors
predictive biomarkers - Answers :-status of the biomarker predicts/determines how the
disease will respond to different therapies
-if biomarker X is present, the disease will reliably respond positively or negatively to the
treatment Y
-mutations with targeted therapy (therapy will be beneficial or not to the disease)
,issues with therapies and treatments - Answers :-efficacy of therapies almost alway
derived from population data/stats
-a percent of the pop will not experience therapy benefit - therefore they are at risk for
therapy side effects
targeted therapy - Answers :-specific therapy that takes advantage of disease
associated biomarkers
-substratify the treatments for the same disease based on the biomarkers that an
individual possesses
-it is targeted because the biomarker is usually only associated with the disease and the
normal tissue is less affected
types of targeted therapies - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-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 - Answers :-activating point mutations
-copy number amplification
-translocations and fusions
tumor suppressor genes - Answers :-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 - Answers :-two different inactivations to destroy gene
loss of heterozygosity - Answers :-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 - Answers :-frameshift mutations
-in/dels (lead to frame shift)
-copy number changes - whole gene deletions
Single nucleotide variants - Answers :-mutation that changes one base (reference) for
another (variant)
transition mutation - Answers :SNV that changes purine to purine or a pyrimidine to a
pyrimidine (A or G to C or T)
Transversion mutation - Answers :SNV that changes purine to pyrimidine or a
pyrimidine to a purine (A to T or C)
synonymous mutation - Answers :-SNV that does not change the coded amino acid
missense mutation - Answers :SNV that causes a change in the coded amino acid
nonsense/stopgain mutation - Answers :-SNV that introduces a stop codon
stopless mutation - Answers :SNV that removes a stop codon
Single nucleotide polymorphism - Answers :-not the same as SNV/point mutations
