Myriad Phase 1 Flashcards
T/F: An autosome is any of the numbered chromosomes, as opposed to the sex chromosomes.
True
T/F: All of our tests utilize next-generation sequencing technology.
True
T/F: In the case of an autosomal dominant condition, an individual must inherit two separate mutations to show symptoms of that condition.
False
T/F: In the case of an x-linked condition, an individual must inherit at least one mutation on an autosome to show symptoms of that condition.
False – Women usually don’t show symptoms, since they have two X chromosomes, so if they inherit one mutation they don’t usually show symptoms. Since men only have one X, one x-linked gene mutation will indeed show symptoms.
T/F: Screening tests can be used to identify individuals out of the general population that may be at increased risk for a particular condition.
True
T/F: Diagnostic tests cannot be used to identify or rule out the presence of a particular condition.
False
T/F: The “New OB visit” is an excellent opportunity for providers to discuss expanded carrier screening and hereditary cancer screening with their patients.
False
T/F: The “Well Woman Visit” is an excellent opportunity for providers to discuss expanded carrier screening and non-invasive prenatal screening for their patients.
False
T/F: You will often find genetic counselors working within Maternal Fetal Medicine practices.
True
T/F: OBGYNs specialize in managing high risk pregnancies such as those with ultrasound abnormalities, placental and growth insufficiency, and mother with diabetes or high blood pressure.
False
T/F: MFM providers will often discuss screening tests such as amniocentesis and chorionic villus sampling with their patients.
False
T/F: Expanded carrier screening, ultrasound, and screening for aneuploidy may be performed either by the obgyn provider or the MFM provider.
True
T/F: patients often self-refer to IVF providers and select a practitioner based on their reputation and success rates.
True
T/F: Within an IVF office, you may find a Reproductive Endocrinologist, an Embryologist, and a Donor Bank/Donor Coordinator.
True
T/F: An autosome is any of the numbered chromosomes, as opposed to the sec chromosomes.
True
T/F: All of o ur testing is completed via next generation sequencing.
True
T/F: In the case of an autosomal dominant condition, and individual must inherit two separate mutations to show symptoms of that condition.
False – In an autosomal dominant disorder, the mutated gene is a dominant gene located on one of the nonsex chromosomes (autosomes). You need only one mutated gene to be affected by this type of disorder. A person with an autosomal dominant disorder has a 50% chance of having an affected child with one mutated gene (dominant gene) and a 50% chance of having an unaffected child with two normal genes (recessive genes).
T/F: In the case of an X-linked condition, an individual must inherit at least one mutation on an autosome to show symptoms of that condition
False
T/F: Screening tests can be used to identify individuals out of the general population that may be at increased risk for a particular condition.
True
T/F: Diagnostic tests cannot be used to identify or rule out the presence of a particular condition.
False
In a female BRCA1 positive patient, MRI’s should begin at age: [20, 25, 30 or 40?]
25
Bilateral Salpingo-Oophorectomy has been shown to reduce an ovarian cancer risk in a BRCA positive patient by as much as: [63%, 75%, 96%, or 100%?]
96%
Colonoscopy can reduce colon cancer by ___% and overall mortality by ___%: [20,30; 25,50; 50,65; 71,82?]
50, 65
In a patient with Lynch Syndrome, adenoma to cancer progression can take: [1-3 years, 5-10 years, or Unknown]
1-3 years
T/F: Clinically, patients with a VUS are manages as a negative.
True
T/F: The purpose of a screening test is to help you identify a target population, within a larger population
True
T/F: False positive and false negative results are possible, and can be expected, with screening tests.
True
T/F: Sensitivity is the % of patients without the disease that receive a negative result (# true negative // # unaffected)
False
T/F: Positive predictive value (PPV) is the chance that a positive result is a true positive
True
T/F: Screening for aneuploidy is offered during pregnancy because diagnostic testing can carry a small risk for pregnancy loss
True
T/F: Diagnostic tests allow for the production of a karyotype to determine if the correct number of chromosomes is present in a fetus
True
T/F: Ultrasound markers were added to maternal serum screening in 2010 to increase the detection rates.
False
T/F: Maternal serum screening involves the analysis of particular hormone or chemical levels in a pregnant mothers’ blood to determine the risk for specific chromosome conditions.
True
T/F: A quad screen involves testing for AFP, estirol, inhibinA, and measuring the nuchal translucency.
False
T/F: Integrated screening, Sequential screening and Contingent Screening are all variations on tests which combine blood work and ultrasound measurements taken in the second and third trimesters of pregnancy
False
T/F: Cell-free DNA screening allows for the separation and analysis of fetal DNA fragments in a pregnant mothers blood
False
T/F: Cell-free DNA screening can be performed any time after 10 weeks gestation
True
T/F: First trimester screening will provide information on open neural tube defects, such as spina bifida.
False
T/F: All forms of maternal serum screening provide information on sex chromosome aneuploidies, such as Turner syndrome.
False
T/F: Maternal serum screening is known to have a false positive rate of approx 5%
True
T/F: Some providers continue to use maternal serum screening and other forms of testing because they believe in the value of “off label” information provided by these options.
True
T/F: Most providers will choose one screening modality and use that one exclusively.
False
T/F: One of the key places of info you will need in planning to sell NIPS to a provider is understanding what they are currently offering to their patients and why.
True
In a poster presented at CGA in 2013, ___% of patients tested for HBOC also met NCCN criteria for Lynch Syndrome and ____% of patients tested for Lynch Syndrome met NCCN criteria for HBOC? [10, 50; 25,75; 7, 29; 15,20]
7, 29
T/F: Myriad myRisk Test Report summary of management recommendations are provided ONLY for positive patients.
False
A RED BAR on the Myriad myRisk Test Result indicates which of the following: [Elevated Risk; No Mutation was found in the genes tested; A genetic mutation was found in one or more of the genes tested; It is not known if the change is associated with an increased cancer risk.]
A genetic mutation was found in one or more of the genes tested.
T/F: Majority of the genes on myRisk have established NCCN or consensus management guidelines
True
Research suggests that Myriad provides a definitive result for __% of variants that would have been classified a VUS at other labs. [5; 10; 45; 90.]
45
Approx, what % of eligible women who test negative on myRisk will have a riskScore . [20%? 25%, 33%, 50%, 66%?]
33%
Approx, ___% of patients pay $0. [25: 33: 75: 100.]
75
Providers can complete a test request form online using the following: [Hereditary Cancer Quiz, MyriadPro, Google.]
MyriadPro
SNP stands for: [Small Nucleotide Polymorphism, Single Nucleotide Polymorphism, Single New Polymorphism, Scottish National Primates.]
Single Nucleotide Polymorphism
A single nucleotide polymorphism is a variation of one nucleotide at a single position in the DNA sequence that occurs in greater than __% of a certain population? [1%, 3%, 5%, 20%]
1%
Although Myriad uses the term polymorphism to refer to a benign genetic variation, in the strict definition of the term, not all polymorphisms are benign. T or F?
True
SNPs are generally associative of a disease, not causative. T or F?
True
A SNP association found in a specific population can be generalized to all populations. T or F?
False
SNPs can be associated with an increased or decreased risk of developing a certain disease. T/F?
True
In Mavaddat study discussed in this module, 77 breast cancer associated SNP’s were evaluated to contruct a scoring system referred to as the: [Lifetime Risk, Mavaddat Score, Polygenic Risk Score, Breast Cancer Risk]
Polygenic Risk Score
The findings from the Mavaddat study showed that the use of SNP analysis to generate a Polygenic Risk Score could help stratify breast cancer risk only in patients with a family history of breast cancer. T/F?
False
riskScore is a breast cancer risk prediction tool that provides women who are unaffected with breast cancer a remaining lifetime and 5-year calculation of their breast cancer risk. T/F?
True
riskScore is based on an analysis of:
[Genetic markers, personal clinical risk factors, and family history of cancer.
Claus and genetic markers
Personal clinical risk factors and family history of cancer
Genetic markers and family history of cancer]
Genetic markers, personal clinical risk factors, and family history of cancer.
Using the data of over 11k patients training study, Myriad was able to generate a single risk estimate using over ___ of the most useful genetic markers showing a consistent association with breast cancer risk. This set of genetic markers and the formula for estimating risk was validated in a study of over ___ could highly predict a breast cancer risk in a high risk patient population.
[50, 10,0000
70, 11,000
75, 15,000
80, 17,000]
80, 17,000
The Hughes study showed that the genetic markers used in the residual risk score (RRS) were highly predictive of breast cancer risk in women with and without a family history of breast cancer. T/F?
True
In order to receive a riskScore, a woman must meet the following criteria:
Be under the age of 85 of solely European ancestry
Have no personal history of breast cancer
Have no personal history of LCIS, Atypical Hyperplasia, or Hyperplasia, or a breast biopsy with unknown results.
Have no known breast cancer related gene mutation or any blood relatives with a breast cancer related gene mutation.
All of the above
All of the above
Patients who have tested positive for a non-breast cancer-related gene mutation such as MLH1 are not eligible to receive a riskScore. T/F
False
A ______ will appear when the patients remaining lifetime risk is at or above 20%?
Blank
Orange asterisk
Green negative
Red positive
Orange asterisk
riskScore will be reported as:
An average risk
Remaining lifetime and 5-year risk
10 year risk
An absolute risk
Remaining lifetime and 5-year risk
Medical management for patients who have both a riskScore and a Tyrer-Cuzick risk estimate of 20% or higher will be based on Tyrer-Cuzick. T/F?
True
Although NCCN and the ACS do not currently provide specific medical management guidelines based on riskScore or other polygenic tests, a riskScore of 20% or higher warrants consideration of medical management. T/F?
True
Which risk model is replacing Claus as the tool myRisk uses to assess a woman’s risk of breast cancer based on family history and clinical risk factors?
[Tyrer-Cuzick, BOADICEA, BRCAPRO, Gail]
Cuzick
What addtl information needs to be collected on the TRF in order to report a Tyrer-Cuzick risk estimate?
[Height/weight, Age of first menstrual period, menopausal status, parity and age of first live birth, hormone replacement therapy use, breast biopsy history, all of the above]
All of the above
What happens if the breast cancer risk model information is incomplete? [use average population data, an estimate wont be reported, Claus will be reported instead]
If certain info required to run Tyrer Cuzick is not provided on the TRF, the model will substitute average population data.
The breast cancer risk model information must be completed for:
[men, women with breast cancer, women who have never been diagnosed with breast cancer, women who have survived breast cancer]
Women who have never been diagnosed with breast cancer
In addition to cancer family history, Tyrer Cuzick considers hormonal and pathologic risk factors in its risk estimate T/F?
True
Tyrer-Cuzick incorporates BRCA 1/2 genetic results into its risk calculation T/F?
True
Tyrer-Cuzick has been shown in some independent studies to be the most consistently accurate breast cancer risk model T/F?
True
Tyrer-Cuzick considers cancer information for affected and unaffected relatives in its risk estimate T/F?
True
How will the Tyrer-Cuzick risk estimate be reported on the MMT?
[As a remaining lifetime risk and a 5-year estimate, as a lifetime risk, as a remaining lifetime risk, As >20% or <20%
As a remaining lifetime risk and a 5 year estimate
NCCN recommends the consideration of MRI in addition to mammogram for women with >20% lifetime risk of breast cancer as defined by models that are largely dependent on family history. T/F?
True
The myRisk mgmt tool will provide medical mgmt recs based on remaining lifetime risk. T/F?
True
A woman who has reported a relative that has been diagnosed with a breast cancer related gene mutation will receive a Tyrer-Cuzick risk estimate, T/F?
False
T/F: We expect that most people have one copy of each gene.
False
T/F: Carrier screening tests for single gene disorders.
True
T/F: Most of the conditions on the Foresight Carrier Screen are autosomal dominant disorders.
False
T/F: In general, a woman who is a carrier of an X-linked condition has a 50% chance to pass that disorder on to each of her sons.
True
T/F: One of the many reasons that expanded carrier screening make sense today is that the population of multi-racial Americans is growing 3x faster than the population as a whole.
True
T/F: 80% of the children born with a genetic disease have no family history of that condition.
True
T/F: ACOG guidelines now state that screening for cystic fibrosis and fragile X syndrome are recommended to be offered for all patients.
False
T/F: ACOG has outlined suggested disease inclusion criteria which aligns with our panel design
True
T/F: Disease selection criteria for the Foresight Carrier Screen include severity, actionability, prevalence, and sensitivity.
True
T/F: All diseases on the Foresight Carrier Screen are associated with shortened life expectancy.
False
Maximizing the detection of at-risk couples is the top priority for carrier screening.
True
The Foresight Carrier Screen provides >99% detection for carriers of cyctic fibrosis
True
T/F: The Foresight Carrier Screen includes custom assays for difficult to sequence genes.
True
T/F: Fragile X and spinal muscular atrophy are examples of difficult to sequence genes on the Foresight Carrier Screen
True
T/F: When managing competitive discussions, I should proactively bring up specific competitors.
False
T/F: When managing competitive discussions, I should ask probing questions to understand the provider’s needs.
True
T/F: Sema4, Natera and Invitae are clinically driven competitors.
True
T/F: Convenience and ease of use are often cited by customers as reasons to select LabCorp/Integrated Genetics and Quest due to a single point of contact for all testing needs and patient service centers.
True
T/F: Labs using a targeted genotyping platform report results from a select set of mutations, whereas full exon sequencing identifies all disease causing mutations within a gene.
True
T/F: MWH has taken a thoughtful approach to designing Foresight, prioritizing serious, prevalent and actionable conditions.
True
Which of Foresights’ competitors also use full exon sequencing?
Netera, Sema4 and Invitae
Expanded Carrier Screening (ECS) is defined as __ or more conditions on a carrier screening panel
15
Sema4 and Invitae have higher at-risk couple detection rates due to their larger panel sizes. T/F
False
T/F: Foresight has an overall at-risk couple detection rate of 4.5% (1 in 22 couples) leading the industry in helping providers identify couples at-risk for serious and actionable conditions.
True
T/F: Basic Carrier Screening (BCS) is defined as 10 or fewer conditions on a carrier screening panel.
False (15 or less)
How many diseases have been carefully selected to be included on the Foresight panel screen?
176
Approx 1 in ____ couples is expected to be identified as “at risk” for one of the conditions included on the Foresight Carrier Screen.
22
The three main messages you can share with your providers to instill their confidence in the Foresight Carrier Screen are “panel with purpose”, “leadership with legacy”, and “complete practice support”. T/F
True
What is a SNP?
A single-nucleotide polymorphism is a substitution of a single nucleotide that occurs at a specific position in the genome, where each variation is present at a level of more than 1% in the population.
Fundamental, Fundamental Plus, and Universal are examples of our ____ screen.
Foresight
What do we test for on the Fundamental Foresight panel?
CF, SMA, and Fragile X
How many conditions do we test for on the Fundamental Plus Foresight panel?
14
Preconception testing maximizes reproductive options and informs pregnancy management to improve outcomes. T/F
True
77% of at-risk couples identified pre-conception change reproductive planning. T/F
True
What did we look for when we designed the Foresight panel?
Severity, actionability, prevalence, and sensitivity.
One in _____ births are affected with one of the conditions we screen for on our Universal panel.
300
Next Gen Sequencing is the tool we use for myRisk, Foresight, and Prequel. T/F
True
One in ______ couples screened with the Foresight Universal Panel is identified to be at risk of having a child affected with a condition on the panel.
22
_____% of at-risk couples identified pre-conception change reproductive planning.
77%
Preconception testing maximizes reproductive options and informs pregnancy management to improve outcomes. T/F
True
The chance a test will find a mutation (gene change) in an individual that has a mutation is the definition of ___________ rate.
Detection rate
The most common inheritance pattern for conditions on a carrier screening panel is __________ recessive. Mutations must be present in both copies of a gene in order for the gene to develop. Carriers with a single mutation typically do not show symptoms.
Autosomal Rescessive
This is a couple known to be at risk to have a child with a genetic condition following a carrier screening.
ARC – At risk couple
T/F: Full exon sequencing is a technique that looks at the entire exon to identify all disease-causing mutations. This technique will detect more disease causing mutations than targeted genotyping, which focuses only on specific areas of the exon where a smaller subset of mutations are known to be associated with a disease. The detection rate of targeted genotyping can vary based on ethnicity, whereas, detection rates for full exon sequencing do not.
True
Copy number variants (CNVs) involve a deletion or duplication of genetic material. A deletion (Del) is a type of mutation involving the loss of genetic material. It can be small, involving a single missing DNA base pair, or large, involving a piece of a chromosome. A duplication (Dup) is a type of mutation that involves the production of one or more copies of a gene or region of a chromosome. Deletions and Duplications are types of copy number variants (CNVs). T/F?
True
What are the names of the two basic carrier screening panels we offer with Foresight?
Fundamental (cycstic fibrosis, spinal muscular atrophy and Fragile X) and Fundamental Plus (14 conditions recommended by ACOG)
How many gene disorders are we testing for on our Universal panel?
176
T/F: 1 in 60 couples screened with the Foresight Fundamental Plus Panel is identified as at elevated risk for a pregnancy affected by a serious inherited condition.
True
What is our detection rate across ethnicities for Foresight?
> 99%
How many years does it typically take for a child to be diagnosed with a rare genetic disease (the kind we screen for with Foresight)?
8 years
_____% of myRisk tests identify a change in medical management
54%
What does NCCN stand for?
National Comprehensive Cancer Network
What is a BSO?
Bilateral Salpingo Oophorectomy– the surgery to remove the ovaries and fallopian tubes. (removal of one ovary and one fallopian tube is called unilateral salpingo-oophorectomy.)
What is VUS?
Variant of uncertain significance – a change in a gene identified through genetic testing, but whose significance to the function or health of an individual is not known.
What is HBOC?
Hereditary Breast and Ovarian Cancer. The genetic basis of Hereditary Breast and Ovarian Cancer syndrome (HBOC) is an inherited mutation in either the BRCA1 orBRCA2 genes
Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is the most common of the hereditary colon cancer syndromes and is believed to account for 3% to 5% of all colorectal cancers. T/F?
True
Approx 1 in ___ patients in the community OBGYN setting are appropriate for hereditary cancer testing.
4
What does WGS stand for?
Whole Genome Sequencing
Identify the different NIPS Methods.
Whole genome sequencing (WGS), Single Nucleotide Polymorphism (SNP) , Microarray quantification.
T/F: Non-invasive prenatal screening is the only screening modality that can provide information on sex chromosome aneuploidies.
True
T/F: NIPS has the lowest false-positive rate of all screening modalities.
True
T/F: All women should be offered the option of aneuploidy screening or diagnostic testing for fetal genetic disorders, regardless of maternal age.
True
T/F: Guidelines recommend that testing for microdeletion syndromes be routinely performed via NIPS.
False – it is offered with Prequel but not recommended for routine use by ACOG (at this time, 2019).
T/F: The Prelude Prenatal Screen utilizes a SNP-based platform for testing.
False
T/F: The resolution of a no-call or failed NIPS result can delay a patient receiving valuable information by 3-6 weeks.
True
T/F: PPV is influenced by maternal age and paternal age.
False – paternal age doesn’t matter for PPV.
T/F: For clarity, PPV is included on the report as a percentage only.
False – PPV is included as a percentage and also includes more clarifying information.
T/F: You might have to help a provider draw the connection between PPV and the risks reported by older methods of screening such as maternal serum screening.
True
T/F: When managing competitive discussions, it is always important to redirect the conversation back to Prequel (or other Myriad products)
True
T/F: When managing competitive discussions, I should always initiate a conversation about a particular competitor to prove that I know my stuff.
False – never bring up the competitor yourself.
Who are the other key players who offer NIPS?
In order of estimated market share: Natera, LabCorp, Quest, Myriad, Ariosa, Progenity, Bioference, Invitae, Sema4, (others)
Which competitor uses a SNP based platform?
Natera
T/F: Two NIPS labs that offer an alternative testing platform are Natera and Ariosa/Roche.
True
T/F: Two NIPS labs that offer fee-forgiveness or max-out-of-pocket programs are Myriad Women’s Health and LabCorp.
False – Progenity and Ariosa/Roche are known for fee-forgiveness/max out of pocket programs
T/F: One major differentiator in the NIPS space is the calculation and reporting of a personalized positive predictive value and residual risk.
True
T/F: Compared with WGS platforms, SNP-based testing has a lower failure rate.
False – WGS has a lower failure rate than SNP.
T/F: SNP-based testing can differentiate maternal and fetal DNA.
False.
T/F: Zygosity determines if twins are identical or fraternal.
True – this is a selling point Natera uses to differentiate themselves.
T/F: With Prequel, our focus is on market development rather than competitive selling.
False – we are not market share leaders (yet)
T/F: A common scenario you will find with customers is that many offer NIPS only to “high risk” patients only
True
Per 1,000 NIPS performed, what is Natera’s test failure rate?
5.2%
Per 1,000 NIPS performed, what is Prequel’s test failure rate?
0.1%
T/F: Compared with SNP technology, our WGS testing provides fewer test failures, fewer false negatives, and leads to fewer invasive procedures.
True
T/F: Prequel is an effective NIPS choice for patients with low fetal fraction, consanguineous couples, and twin pregnancies.
True
T/F: Guidelines from SMFM, ACOG, and ACMG are expanding to include testing for all patients.
True
T/F: 92% of the consults performed by our genetic counselors related to Prequel results are for patients whose pregnancies have tested positive and are at increased risk for chromosome abnormality.
False – 92% represents the percent of consults for NEGATIVE results, which goes to show that women are very anxious about this and a low failure rate is essential to help providers help manage their patients care.
T/F: Price estimates are particularly important fo rthe general OB population, including “average-risk” patients.
True
What is the general population risk for breast cancer?
12-15%
What is the hereditary risk of breast cancer?
87%
What is the general population risk for ovarian cancer?
0.7%
What is the hereditary risk of ovarian cancer?
63%
What is the general population risk for colon cancer?
3.4%
What is the hereditary risk for colon cancer with Lynch Syndrome?
82%
What is the general population risk for endometrial cancer?
1.6%
What is the hereditary risk of endometrial cancer?
71%
T/F: The focus of non-invasive prenatal screening is on identifying differences in the number and/or structure of chromosomes.
True
Typical human cells contain ___ pairs of chromosomes.
23 pairs
What is the purpose of Prequel prenatal screening?
To provide actionable information to families seeking insight into the health of their pregnancy – it is NOT prevention.
T/F: In order to obtain a true diagnosis for a pregnancy, a procedure such as amniocentesis or chorionic villus sampling must be performed.
True
How many years experience does Myriad have in BRCA hereditary testing?
27
What is the familial risk of breast cancer?
40%
What is the familial risk of ovarian cancer?
11%
What is the familial risk of colorectal cancer?
20%
What is the familial risk of endometrial cancer?
4%
