Trigger 9 - Epigenetics and Lung cancer Flashcards
Define Epigenetics
Epigenetics refers to the modifications to DNA which alter how the DNA is used, but do not alter the underlying genetic sequence.
What factors can alter epigenetics?
A) Genetic mutations
B) Environmental factors
C) Physical exercise
D) All of the above
B) Environmental factors
DNA methylation involves the addition of a ____ group to cytosine residues in the DNA sequence.
methyl (CH3)
True or False:
CpG sites are distributed equally across the genome.
False
Describe Tissue Specificity of DNAm Patterns
DNA methylation has tissue and cell-specific patterns at certain CpG sites. This can confound results of research studies if not accounted for. During study design, it’s critical to consider disease-relevant tissues/cells.
Which of the following is enriched in regulatory elements and clusters CpG sites?
A) CpG islands
B) Tandem repeats
C) Telomeres
D) Introns
A) CpG islands
CpG sites cluster in CpG-rich regions called ___.
CpG islands
True or False:
DNA methylation patterns are consistent across all tissues and cells.
False
Define DNAm
DNA methylation involves the addition of a methyl group (CH3) to cytosine residues in the DNA sequence.
How many DNAm-based assays are available to predict treatment response?
A) One
B) Three
C) Five
D) Ten
C) Five
Understanding subtype informs ___ and ___ strategy.
prognosis; treatment
True or False:
Assays for prediction of treatment response using DNAm always involve tumor biopsies.
True
Define DNA Methylation
DNA methylation involves the addition of a methyl group (CH3) to cytosine residues in the DNA sequence.
Where does the majority of DNA methylation (DNAm) occur?
A) Adenine residues
B) Guanine residues
C) Thymine residues
D) Cytosine residues
D) Cytosine residues
CpG sites are not distributed equally across the ____.
genome
True or False:
CpG islands are CpG-poor regions.
False
Describe Tissue Specificity of DNAm Patterns
DNA methylation exhibits tissue and cell-specific patterns at certain CpG sites. Failure to account for this specificity can lead to skewed research results. Researchers must consider disease-relevant tissues/cells during study design.
Which of the following factors can DNA methylation patterns be altered by?
A) Moon phases
B) Solar flares
C) Environmental factors
D) Time of day
C) Environmental factors
DNA methylation has tissue and ____ specific patterns at certain CpG sites.
cell
True or False:
Understanding subtype does not impact prognosis or treatment strategy.
False
Define Personalized Medicine:
Personalized medicine involves tailoring medical treatment to the individual characteristics of each patient.
What is the Heidelberg classifier used for?
A) Identifying plant species
B) Predicting response to cancer treatment
C) Determining blood type
D) Predicting weather patterns
B) Predicting response to cancer treatment
True or False:
DNAm-based assays for predicting treatment response never require tumor biopsies.
False
Define MGMT:
MGMT is a DNA repair enzyme whose methylation status in glioblastoma tumors predicts a favorable response to alkylating agents such as carmustine/BCNU or temozolomide.
What type of tumors is MGMT promoter methylation status recommended to be tested in according to NCCN guidelines?
A) Grade 1/2 gliomas
B) Grade 3/4 gliomas
C) Breast tumors
D) Lung tumors
B) Grade 3/4 gliomas
MGMT methylation status in glioblastoma tumors predicts a favorable response to ____ agents.
alkylating
True or False:
MGMT methylation status is not associated with response to alkylating agents.
False
Describe PITX2
PITX2 methylation status in breast cancer tumors predicts response to adjuvant anthracycline-based chemotherapy in patients with high-risk breast cancer. It has also been shown to predict the risk of distant metastases in breast cancer. PITX2 is a transcription factor involved in pituitary-specific gene regulation and left-right patterning in embryonic and organogenic development.
Which type of chemotherapy does PITX2 methylation status predict response to in breast cancer?
A) Platinum-based
B) Taxane-based
C) Anthracycline-based
D) Antimetabolite-based
C) Anthracycline-based
One CE-marked test available for PITX2 methylation status is the Therascreen PITX2 RGQ PCR assay from ___.
Qiagen
Define Epi-ASCENT Project
The Epi-ASCENT project aims to identify DNA methylation signatures of aggression and indolence in LDCT-detected lung cancers by comparing fast and slow-growing tumors identified as part of the ASCENT study.
What is the main objective of the ASCENT study?
A) To analyze molecular and cellular signatures of breast cancer
B) To assess if low dose CT scans could improve early detection of lung cancers
C) To investigate the efficacy of chemotherapy in treating lung cancer
D) To study the effects of smoking on lung health
B) To assess if low dose CT scans could improve early detection of lung cancers
The SUMMIT study, established in 2017, aimed to assess if low dose CT scans could improve early detection of lung cancers. The ASCENT study, established in 2020, aims to analyze the molecular and cellular signatures of ____-detected lung cancers.
screen
True or False:
The Epi-ASCENT study aims to identify DNA methylation signatures of aggression and indolence in LDCT-detected lung cancers.
True
Describe Epi-ASCENT Projec
The Epi-ASCENT project aims to identify DNA methylation signatures of aggression and indolence in LDCT-detected lung cancers by comparing fast and slow-growing tumors identified as part of the ASCENT study.
From which study were patients recruited for the Epi-ASCENT project?
A) Epi-ASCENT study
B) SUMMIT study
C) ASCENT study
D) META study
B) SUMMIT study
Patients recruited for the Epi-ASCENT project were aged -.
55-77
True or False:
Patients recruited for the Epi-ASCENT project must currently be diagnosed with cancer.
False
What is the first aim of the Epi-ASCENT project?
A) To assess the effects of chemotherapy in treating lung cancer
B) To identify de novo tumor methylation signatures of aggression and indolence
C) To study the efficacy of radiation therapy in lung cancer patients
D) To analyze the molecular and cellular signatures of breast cancer
B) To identify de novo tumor methylation signatures of aggression and indolence
Epi-ASCENT aims to identify de novo tumor methylation signatures of aggression and indolence in LDCT-detected lung cancers by comparing fast to slow-growing tumor sub-groups identified in the ____ study.
Ascent
True or False:
One of the aims of Epi-ASCENT is to assess the methylation-based smoking and aging signatures of NSCLCs.
True
What is the second aim of the Epi-ASCENT project?
A) To identify de novo tumor methylation signatures of aggression and indolence
B) To analyze the effects of chemotherapy in treating lung cancer
C) To assess the methylation-based smoking and aging signatures of NSCLCs
D) To investigate the role of immune cells in lung cancer progression
C) To assess the methylation-based smoking and aging signatures of NSCLCs
Epi-ASCENT aims to assess the methylation-based smoking and aging signatures of NSCLCs, and test if these correlate with ____ rate.
Growth
True or False:
Epi-ASCENT aims to use integrated genomic analyses to combine epigenetic data, RNA-seq, and whole exome sequencing data to understand the role of genetics in tumor suppression and progression.
False
What is the third aim of the Epi-ASCENT project?
A) To assess the effects of chemotherapy in treating lung cancer
B) To identify de novo tumor methylation signatures of aggression and indolence
C) To use integrated genomic analyses to understand the role of epigenetics in tumor suppression and progression
D) To analyze the effects of radiation therapy in lung cancer patients
C) To use integrated genomic analyses to understand the role of epigenetics in tumor suppression and progression
True or False:
Epi-ASCENT aims to test if smoking and aging signatures correlate with growth rate in lung cancers.
True
Define Multi-omics Approach
his refers to performing analyses that combine more than one type of data (or ‘omics’), such as genetic sequencing (genomics), DNA methylation assessment (epigenomics), and measurement of gene expression levels of genes (transcriptomics).
What does the term “multi-omics approach” refer to?
A) Analyzing multiple diseases simultaneously
B) Using multiple data types in research analysis
C) Performing surgery on multiple patients at once
D) Combining multiple treatments in medical practice
B) Using multiple data types in research analysis
Multi-omics approach combines data from genetic sequencing (genomics), DNA methylation assessment (epigenomics), and measurement of gene expression levels of genes (____).
transcriptomics
True or False:
Multi-omics approach aims to analyze only one type of data at a time.
False
What is the purpose of combining DNAm with RNA-seq data?
A) To identify genetic variants associated with methylation sites
B) To test if growth-rate related DMP signatures correlate with differences in gene expression
C) To assess patient response to treatment
D) To analyze tumor morphology
B) To test if growth-rate related DMP signatures correlate with differences in gene expression
Combining DNAm with RNA-seq aims to test if growth-rate related DMP signatures correlate with differences in gene expression identified in ___.
RNA-seq
True or False:
The combination of DNAm with RNA-seq aims to analyze differences in tumor morphology.
False
What does WES stand for in this context?
A) Whole Exome Sequencing
B) Whole Epigenome Sequencing
C) Western Blotting and Electrophoresis
D) Whole Environmental Surveillance
A) Whole Exome Sequencing
Combining DNAm with WES aims to identify meQTLS, which stands for ___.
methylation quantitative trait loci
True or False:
Methylation sites associated with genetic variants are not identified through the combination of DNAm with WES.
False
hat is one potential patient impact of combining DNAm with other techniques, according to the provided information?
A) Development of invasive diagnostic methods
B) Improved understanding of tumor morphology
C) Development of non-invasive methods to predict tumor growth rate
D) Identification of non-specific therapy targets
C) Development of non-invasive methods to predict tumor growth rate
True or False:
Combining DNAm with other techniques does not contribute to the understanding of molecular causes of tumor aggression.
False
Potential Benefits of Taking Part in SUMMIT
Early detection: participation offers the potential of early detection of cancer, which can significantly improve treatment outcomes and survival rates.
Access to Advanced Screening Technologies: state-of-the-art screening technologies that may not be available outside of clinical trial settings.
Contributing to Medical Science: contribution to advancing scientific knowledge in developing diagnostic tools.
Monitoring and Follow-up: Regular monitoring and care may lead to early detection of other health issues (other than cancer).
Financial compensation: SUMMIT study provides £20 shopping voucher per follow-up.
What is one potential benefit of participating in clinical trials such as SUMMIT?
A) Increased risk of side effects
B) Access to advanced screening technologies
C) Uncertainty of risk
D) Limited access to individual results
B) Access to advanced screening technologies
Participating in SUMMIT offers the potential of early detection of cancer, which can significantly improve treatment outcomes and ___ rates.
Survival
True or False:
Participants in SUMMIT may contribute to advancing scientific knowledge in developing diagnostic tools.
True
Potential Disadvantages of Taking Part in SUMMIT:
ncertainty of Risk: Inherent risk of unknown side effects (from LCDT scans etc.).
Time and Commitment: Significant commitments involving multiple clinic visits and follow-up appointments.
Emotional Impact: fear and anxiety associated with cancer screening and diagnosis.
Limited Access to Individual Results: Participants may not receive individual test results depending on the stage of development.
What is one potential disadvantage of participating in clinical trials such as SUMMIT?
A) Financial compensation
B) Access to advanced screening technologies
C) Emotional impact associated with cancer screening and diagnosis
D) Contribution to advancing scientific knowledge
C) Emotional impact associated with cancer screening and diagnosis
Participants in SUMMIT may face uncertainty of risk due to the inherent risk of unknown side effects from ____ scans.
LDCT
True or False:
Participants in SUMMIT may have limited access to individual test results depending on the stage of development.
True
Define DNA Methylation
DNA methylation (DNAm) involves the addition of a methyl group (CH3) to cytosine residues in DNA.
What is DNA methylation?
A) Addition of a phosphate group to cytosine residues
B) Addition of a methyl group to cytosine residues
C) Removal of adenine residues from DNA
D) Addition of a hydroxyl group to thymine residues
B) Addition of a methyl group to cytosine residues
Majority of DNA methylation occurs at ___ sites.
CpG
True or False:
DNA methylation is not affected by genetics and lifestyle factors.
False
Tissue Biopsies (Method, pro, con)
Method: Extraction and analysis of sample cells/tissue.
Advantages: Gold standard for cancer profiling, easier to determine tumor-specific variants.
Limitations: Invasive, time-consuming, may not account for tumor heterogeneity.
Liquid Biopsies (Method, pro and cons)
Method: Sampling and analysis of biological fluids (blood, urine, saliva, etc.).
Advantages: Quick, easy to administer, minimally invasive, highly repeatable for regular screening.
Limitations: Higher likelihood of false negatives, not currently reproducible for all cancer types.
Which method involves the extraction and analysis of sample cells/tissue?
A) Tissue biopsies
B) Liquid biopsies
C) Nanopore sequencing
D) Bisulphite sequencing
A) Tissue biopsies
Liquid biopsies involve sampling and analysis of ___ fluids.
Biological
True or False:
Liquid biopsies are invasive and time-consuming.
False
Multiple Choice:
Which biomarker reflects genetic alterations?
A) CTCs
B) cfDNA
C) ctDNA
D) Exosomes
C) ctDNA
True or False:
microRNAs are specific to tumors and not influenced by other conditions.
False
What is a method used in methylation arrays?
A) PCR amplification
B) Bisulphite conversion of genomic DNA
C) Gel electrophoresis
D) Western blotting
B) Bisulphite conversion of genomic DNA
Methylation Arrays (Illumina 450k/EPIC) (method, pro and cons)
Method: Bisulphite conversion of genomic DNA, fluorescent staining, array scanning.
Pros: High sensitivity, time-effective, user-friendly, suitable for clinical samples.
Cons: Only detects previously determined regions, biased towards known CpG sites, affected by polymorphisms.
What is a method used in methylation arrays?
A) PCR amplification
B) Bisulphite conversion of genomic DNA
C) Gel electrophoresis
D) Western blotting
B) Bisulphite conversion of genomic DNA
True or False:
Methylation arrays are not suitable for clinical samples.
False
Nanopore Sequencing (method, pro and con)
Method: Direct detection of DNA through nanopore sensors.
Pros: Single nucleotide resolution, real-time analysis, reproducible.
Cons: Limited sequencing accuracy, context-dependent sequencing bias, higher cost.
What is a characteristic of nanopore sequencing?
A) Low sequencing accuracy
B) Indirect detection of DNA
C) Real-time analysis
D) Low cost
C) Real-time analysis
Nanopore sequencing allows direct reading of long nucleotide sequences and identification of modifications to the ___.
nucleotide
True or False:
Nanopore sequencing has limited sequencing accuracy.
True
Bisulphite Sequencing – Whole Genome (method, pro and con)
Method: Conversion of cytosine to uracil, methylation status determined through direct PCR sequencing.
Pros: Single-nucleotide resolution, whole genome coverage, high accuracy.
Cons: Requires lots of DNA, specialized bioinformatics tools, fresh cell/tissue samples.
What is a characteristic of bisulphite sequencing?
A) Low accuracy
B) Partial genome coverage
C) Conversion of uracil to cytosine
D) Single-nucleotide resolution
D) Single-nucleotide resolution
Bisulphite sequencing requires lots of ___.
DNA
True or False:
Bisulphite sequencing does not require specialized bioinformatics tools.
False