Cancer Genetics Final Exam

The APC I1307K variant is:

a. Associated with Familial Adenomatous Polyposis (FAP)

b. Is not associated with classic FAP

c. Associated with attenuated FAP

d. Associated with Lynch syndrome

b. Is not associated with classic FAP

According to the current NCCN Guidelines, a polyposis syndrome should be considered in any individual with a personal or family history of:

a. 20 or more adenomatous polyps

b. 10 or more adenomatous polyps

c. 100 or more adenomatous polyps

d. 1 serrated polyp/lesion proximal to the rectum

b. 10 or more adenomatous polyps

Mismatch repair proteins are essential for:

a. Controlling cell growth

b. Promoting apoptosis

c. Repairing DNA errors generated during DNA replication

d. Becoming oncogenes, when mutated

c. Repairing DNA errors generated during DNA replication

Which clinical criteria are commonly used to assess whether a patient meets testing guidelines for Lynch syndrome?

a. Amsterdam II Criteria and Revised Bethesda Guidelines

b. NCCN BRCA Testing Criteria

c. Gail Model

d. Cowden Syndrome Diagnostic Criteria

a. Amsterdam II Criteria and Revised Bethesda Guidelines

The word “diffuse” is used to describe gastric cancer that:

a. Is associated with an inherited genetic syndrome most often caused by an inactivating mutation in the E-cadherin gene

b. Causes thickness rather than a mass in the stomach lining

c. Sometimes, is also called “signet ring cell gastric cancer” or “linitis plastica”

d. All of the above

d. All of the above

Of the genes listed below, which of their proteins join to form a dimer involved in identifying errors made during DNA replication:

a. MLH1 and MSH2

b. MSH2 and PMS2

c. MSH2 and MSH6

d. MSH6 and MLH1

c. MSH2 and MSH6

How often do hamartomatous polyps pose a risk for malignancy?

a. Never

b. Rarely

c. Often

d. Always

b. Rarely

Which of the following hereditary cancer syndromes exhibit intussusception?

a. FAP

b. MUTYH-Associated Polyposis Syndrome

c. Juvenile Polyposis Syndrome

d. Peutz-Jeghers Syndrome

d. Peutz-Jeghers Syndrome

When discussing Juvenile Polyposis Syndrome with a patient, it is important to note that:

a. It has an autosomal recessive mode of inheritance

b. The term “juvenile” refers to the age of onset of the polyps

c. Hereditary Hemorrhagic Telangiectasia is present in all affected individuals

d. It is caused by pathogenic variants in the SMAD4 gene or BMPR1A gene

d. It is caused by pathogenic variants in the SMAD4 gene or BMPR1A gene

The autosomal recessive syndrome that is associated with biallelic mismatch repair (MMR) gene mutation is called:

a. Autosomal Recessive Lynch Syndrome

b. Autosomal Recessive Mismatch Repair Deficiency Syndrome

c. Congenital Mismatch Repair Deficiency Syndrome

d. Constitutional Mismatch Repair Deficiency Syndrome

d. Constitutional Mismatch Repair Deficiency Syndrome

Peutz-Jeghers syndrome is characterized by the following except?

a. Gastrointestinal polyps

b. Mucocutaneous pigmentation

c. Juvenile polyps

d. Female sex-cord tumors

c. Juvenile polyps

Healthcare providers should inquire about CHRPE and dental abnormalities while taking a family history, if which of the following hereditary cancer syndromes is part of the differential diagnosis:

a. Familial Adenomatous Polyposis (FAP)

b. MUTYH-Associated Polyposis Syndrome

c. Juvenile Polyposis Syndrome

d. Peutz-Jeghers Syndrome

a. Familial Adenomatous Polyposis (FAP)

Which of the following is not a criterion appropriate for the evaluation of Lynch syndrome?

a. An individual with colorectal tumor displaying microsatellite instability

b. A known Lynch Syndrome-associated pathogenic variant in the family

c. One or more first-degree relative(s) with a colorectal or endometrial cancer and a synchronous or metachronous Lynch Syndrome-related cancer diagnosed at any age

d. Personal family history of a tumor with MMR deficiency diagnosed at any age

d. Personal family history of a tumor with MMR deficiency diagnosed at any age

Amsterdam II criteria includes the following, EXCEPT:

a. 3 or more relatives with a Lynch syndrome cancer

b. 2 or more successive generations

c. 1 or more cancers diagnosed before the age of 50y

d. Tumor showing microsatellite instability

d. Tumor showing microsatellite instability

Which of the following genetic syndromes is most commonly associated with early-onset colorectal cancer and increased risk for endometrial cancer?

a. Familial Adenomatous Polyposis (FAP)

b. Lynch Syndrome

c. MUTYH-Associated Polyposis

d. Peutz-Jeghers Syndrome

b. Lynch Syndrome

Which of the following genes is/are associated with autosomal recessive polyposis syndromes?

a. MSH3

b. MUTYH

c. NTHL1

d. All of the above

d. All of the above

Which of the following IHC results is not suspicious for Lynch syndrome?

a. MLH1 present, MSH2 absent, MSH6 absent, PMS2 present

b. MLH1 present, MSH2 present, MSH6 absent, PMS2 present

c. MLH1 present, MSH2 present, MSH6 present, PMS2 absent

d. MLH1 present, MSH2 present, MSH6 present, PMS2 present

d. MLH1 present, MSH2 present, MSH6 present, PMS2 present

The following statements regarding immunohistochemical (IHC) analysis for Lynch syndrome are true, EXCEPT:

a. IHC is a diagnostic test for Lynch syndrome

b. IHC looks for the presence of proteins in a tumor

c. IHC may help identify individuals with Lynch Syndrome

d. IHC may miss individuals with Lynch syndrome

a. IHC is a diagnostic test for Lynch syndrome

If left untreated, individuals diagnosed with the following syndrome risk of developing colorectal cancer is almost 100%:

a. Peutz-Jeghers syndrome

b. Familial Adenomatous Polyposis

c. Juvenile Polyposis Syndrome

d. Serrated Polyposis Syndrome

b. Familial Adenomatous Polyposis

The following syndromes are inherited in an autosomal recessive manner, except:

a. MUTYH-Associated Polyposis syndrome (MAP)

b. NTHL1-Associated Polyposis

c. Attenuated Familial Adenomatous Polyposis (AFAP)

d. Constitutional Mismatch Repair Deficiency (CMMRD)

c. Attenuated Familial Adenomatous Polyposis (AFAP)

The definition of cancer includes:

a. An abnormal multiplication of cells or tissue

b. A group of diseases

c. A cellular process that can lead to death

d. All of the above

d. All of the above

Modifiable risk factors for cancer include the following, except:

a. Smoking & lifestyle

b. Heredity & ethnicity

c. Alcohol intake

d. Nutrition

b. Heredity & ethnicity

True or False: Incidence is defined as the “Number of new events in a defined population during a specific time-period”?

a. True

b. False

a. True

The main purpose of drawing a pedigree and collecting personal and family history during a cancer counseling session is to:

a. Determine whether the patient has or is at risk for an inherited predisposition to cancer

b. Raise awareness regarding the field of genetic counseling

c. Encourage the patient to undergo testing

d. Persuade the patient to defer testing until has life-insurance

a. Determine whether the patient has or is at risk for an inherited predisposition to cancer

Genetic Counseling for cancer usually includes an evaluation and a discussion of the following, except:

a. The patient’s personal and family’s medical history

b. Genetic testing, if indicated

c. Patient’s cardiac medical history

d. Cancer pathology and ethnic background

c. Patient’s cardiac medical history

True or False: Knudson “Two-Hit Hypothesis” states that most tumor suppressor genes require both alleles to be inactivated.

True

The benefits of genetic testing include:

a. Variants of uncertain significance

b. Discussion of risk-reducing options

c. Uninformative negative results

d. Insurance discrimination

b. Discussion of risk-reducing options

Explain why it may seem like the Hereditary Breast and Ovarian Cancer Syndrome skips a generation, even though it does not:

1. Sex of the inherited carrier:

2. Variable penetrance

3. Prophylactic measures

4. Age-related onset:

Which of the following hereditary cancer syndromes exhibits the highest penetrance?

a. Hereditary Breast and Ovarian Cancer Syndrome

b. Li-Fraumeni Syndrome

c. Peutz-Jeghers Syndrome

d. PTEN Hamartoma Syndrome

a. Hereditary Breast and Ovarian Cancer Syndrome

Genetic counselors should inquire about macrocephaly during the intake if which of the following hereditary cancer syndromes is part of the differential diagnosis:

a. Hereditary Breast and Ovarian Cancer Syndrome

b. Li-Fraumeni Syndrome

c. Peutz-Jeghers Syndrome

d. PTEN Hamartoma Syndrome

b. Li-Fraumeni Syndrome

The following findings are not associated with increased risk for breast cancer except:

a. Ductal carcinoma in-situ

b. Fibroadenoma

c. Calcifications

d. Cysts

a. Ductal carcinoma in-situ

PARP-inhibitors is a class of targeted cancer therapies that:

a. Block the enzyme poly (ADP-ribose) polymerase

b. Commonly used for BRCA1/2 mutated cancer

c. Prevent cancer cells with BRCA1/2 P/LP variants from repairing DNA damage

d. All of the above

d. All of the above

Define the term Familial Cancer.

Familial cancer means cancer that clusters in families, likely due to a mix of genes and environment, but without a clearly identifiable inherited mutation.

Reproductive risks for autosomal recessive conditions should be discussed with patients testing positive for the following genes, except:

a. BRCA2

b. PTEN

c. ATM

d. PALB2

b. PTEN

Genetic heterogeneity refers to:

a. Equal transmission of a pathogenic variant by males vs. females

b. Difference in transmission of a pathogenic variant in males vs. females

c. Mutations in different genes that cause the same disease

d. Different modes or degrees of expression of a trait in a population

c. Mutations in different genes that cause the same disease

Common misconceptions in cancer genetics include all, except:

a. Negative test results mean cancer will never develop

b. Positive test results mean cancer will develop

c. “Female” cancers are only inherited from the maternal side

d. Genetic testing for cancer can guide management and surveillance

d. Genetic testing for cancer can guide management and surveillance

Genetic testing of a tumor may help with which of the following:

a. Determine a tumor’s primary site

b. Determine which drugs a patient may respond to

c. Identify germline variants

d. All of the above

d. All of the above

A diagnosis of invasive lobular breast cancer is a suspicious feature of which hereditary cancer syndrome?

a. Hereditary Breast and Ovarian Cancer Syndrome

b. Hereditary Diffuse Gastric Cancer Syndrome

c. Peutz-Jeghers Syndrome

d. PTEN Hamartoma Syndrome

b. Hereditary Diffuse Gastric Cancer Syndrome

Modifiable risk factors include all, except:

a. Alcohol use

b. Sun exposure

c. Ethnicity

d. Physical activity

c. Ethnicity

Based on the pedigree below, what is the minimal genetic test most appropriate to offer the proband?

a. Breast Cancer Genes Panel

b. Multigene Breast-Gynecological Cancer Gene Panel

c. BRCA2 6174delT

d. Three AJ founder BRCA1 and BRCA2 pathogenic variants

Ethnicity (both sides): AJ

Proband’s mom dx 42 Breast Cr

Proband’s cousin +BRCA2 6174delT

Proband’s aunt dx 53 Ovarian Cr, +BRCA2 6174delT

d. Three AJ founder BRCA1 and BRCA2 pathogenic variants

Here's why:

• Ashkenazi Jewish ancestry on both sides

• A known familial BRCA2 6174delT mutation

• The three AJ founder mutations include:

  • BRCA1 185delAG

  • BRCA1 5382insC

  • BRCA2 6174delT

Why not the other options?

• a. Breast Cancer Genes Panel – broader than needed given that a specific familial variant is known.

• b. Multigene Breast-Gynecological Panel – more extensive and costly; not minimal testing.

• c. BRCA2 6174delT only – would catch the known variant but miss the other two AJ founder variants if present.