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National In-training Exams > Cancer Genetics (TRANSFERRED) > Flashcards

Cancer Genetics (TRANSFERRED) Flashcards

1
Q

Reference: Genetics residents in-training examination - March 2020 (Spring 2020)

Name 5 pancreatic cancer predisposition genes.

A 
BRCA2
PALB2
ATM
CDKN2B, MEN1, CDK4
MLH1, MSH2, MSH6, PMS2, EPCAM
SPINK1, PRSS1, CTRC, CASR
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2
Q

Reference: Genetics residents in-training examination - March 2020 (Spring 2020)

A 39-year-old woman was recently diagnosed with triple-negative breast cancer (an infiltrating ductal carcinoma).

Genetic testing identified heterozygous pathogenic germline mutations in RAD51D and PALB2.

What screening and management recommendations would you give this patient?

A

For PALB2 (risk of breast and pancreatic cancer)

  • discuss bilateral mastectomy for risk reduction
  • explain increased risk for pancreatic cancer and suggest yearly screening by MRI of pancreas
  • explain the higher relative risk of ovarian cancer, but not enough evidence in favour of prophylactic TAHBSO

For RAD51D (risk of breast and ovarian cancer)

  • discuss prophylactic TAHBSO at approximately age 40-50 in order to reduce risk of ovarian cancer (risk 8-12 times baseline)
  • breast follow-up with yearly MRI (no recommendation for prophylactic surgery)

Bonus point if the resident gives combined recommendations that take into account the patient’s clinical situation.

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3
Q

Reference: Genetics residents in-training examination - March 2020 (Spring 2020)

Name 5 cancer predisposition syndromes caused by biallelic mutations.

A 
Fanconi syndrome
Nijmegen syndrome
Ataxia-Telangiectasia
Rothmund-Thomson syndrome
CMMRD ( LYNCH biallelic)
MUTYH biallelic mutation
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4
Q

Reference: Genetics residents in-training examination - March 2020 (Spring 2020)

Name 5 genes associated with cancer predisposition syndromes conferring a risk of malignant tumours both in childhood and in adulthood.

A 
TP53
DICER1
BRCA1 / BRCA2
MLH1, MSH2, EPCAM, PMS2, MSH6
APC
ATM
PALB2
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5
Q

Reference: Genetics residents in-training examination – Fall 2020

List 6 syndromes associated with hereditary predisposition to colorectal cancer and name at least 1 dermatologic manifestation associated with that syndrome.

A
  1. Lynch: Sebaceous adenoma or carcinoma, keratoacanthoma, SCC
  2. BMMRD (Biallelic mismatch repair deficiency): Multiple CAL macules
  3. FAP: Epidermoid cysts, fibroams, desmoid
  4. MAP: Debacouea adenoma or carcinoma, pilomatricoma
  5. Peutz Jegher Syndrome: Pigmented macules of mouth, lips, distal extremities, anogenital region
  6. Juvenile Polyposis: HHT symptoms
  7. PTEN hamartoma syndrome: Tricheilemmoma, papilloma, acral and plantar keratosis, fibromas
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6
Q

Reference: Genetics residents in-training examination – Fall 2020

A 13yo is referred with a HC of >99th percentile and autism. You suspect a diagnosis of PTEN. Your physical exam demonstrates a height at the 98th percentile and weight at the 97th percentile.

A. What would you look for on skin exam to help confirm your hypothesis?

B. You identify a lipoma and vascular lesion. Does the 13yo meet clinical criteria?

C. You take a family history and determine the following; His mother can’t find hats that fit her head, and was diagnosed with breast cancer at age 49, and thyroid cancer at age 51y. Does she meet clinical criteria?

D. To confirm the likely diagnosis in your 13yo patient you initiate PTEN sequencing. A pathogenic mutation is identified. What screening would you implement for him?

E. What cancers is he at risk for as an adult for which there are surveillance guidelines?

F. Historically, what are the names of the two conditions now known to be caused by PTEN?

G. Name two additional overgrowth syndromes.

A

A. (lipomas, trichilemmomas, papillomas, keratoses, penile freckling, vascular features, such as arteriovenous malformations or hemangiomas)

B. No

C. Yes

D. Thyroid US and yearly skin exam

E. Colon, renal, melanoma

F. Cowden syndrome and Bannayan Riley Ruvalcalba.

G. Sotos, Weaver, Beckwith, SGBS, others.

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7
Q

Reference: Genetics residents in-training examination – Fall 2020

List 5 hereditary cancer syndromes where identification of a germline predisposition has a therapeutic impact. Identify associated gene and specify therapeutic impact.

Syndrome Gene Therapeutic Impact

A

List 5 hereditary cancer syndromes where identification of a germline predisposition has a therapeutic impact. Identify associated gene and specify therapeutic impact (_______/10) 0.5 for syndrome and gene, 1 for therapeutic impact

  1. Li Fraumeni = Tp53 = Avoidance radiotherapy
  2. HBOC = BRCA1/2 = Eligibility for PARP inhibitors
  3. Lynch Syndrome = MLH1, MSH2, MSH6, PMS2, EPCAM = Avoidance of 5FU based adjuvant chemotherapy; PD-1 and PD-L1 blockade
  4. Gorlin Syndrome = PTCH1 = Avoidance of radiotherapy; sonic hedgehog antagonists (investigational)
  5. Cowden Syndrome = PTEN = Use of mTOR inhibitors (investigational)
  6. Tuberous Sclerosis = TSC1/2 = Use of mTOR inhibitors (LAM, cardiac rhabdomyoma, facial angiofibroma (topical), intractable epilepsy
  7. NF2 = NF2 = Avoidance radiotherapy
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8
Q

Reference: Genetics residents in-training examination – Fall 2020

You are in the Cancer Genetics Clinic and the 40 year old patient you are about to assess has been referred following the recent resection of a cecal adenocarcinoma. On the referral it is noted that one of his 3 sisters was diagnosed with uterine cancer at age 45 years.

  1. What details from the pathology report are important to consider?
  2. What are the 3 most likely diagnoses?
    Most likely diagnoses:
  3. What testing would you order? Please specify the genes you believe to be most important to include in testing.
  4. What do you estimate the probability of finding a germline mutation to be?
A
  1. Details on his pathology report
    a. IHC staining result if available
    b. Histologic features associated with LS: mucinous/tumour infiltrating lymphocytes/Crohn’s like lymphoid reaction
    c. Associated polyposis if present
  2. a. Sporadic/familial
    b. Lynch syndrome
    c. MUTYH associated polyposis (MAP) or
    d. Polymerase proofreading polyposis (POLE/POLD1)

3.
Testing: Multigene panel
Most important genes: MLH1, MSH2, MSH6, PMS2, EPCAM, MUTYH, POLD1, POLE, PTEN, APC, (Also STK11, BMPR1A, TP53)

  1. Probability of finding a germline mutation: likely 20-25% if use moderate size panel (also accept 15-20% if smaller panel used)
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9
Q

Reference: Genetics residents in-training examination – Fall 2020

List 3 ways that information derived from molecular genetic tumor testing can be used to inform germline genetic testing.

A
  • Tumors that show microsatellite instability are more suspicious for Lynch syndrome (MMR gene mutations)
  • Presence of BRAF V600E in a colon tumor deficient for MLH1 is more likely to be sporadic
  • Presence of MLH1 promoter methylation in a colon or endometrial tumor deficient for MLH1 is more likely to be sporadic
  • Patients with ovarian (or prostate) tumors that are found to have pathogenic BRCA1 or BRCA2 gene mutations are more likely to also have this mutation in their germline.

Note: IHC analysis isn’t molecular genetic test but is used to help direct genetic testing for Lynch syndrome genes.

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10
Q

Reference: Genetics residents in-training examination – Fall 2020

List 6 genes other than BRCA1 and BRCA2 that are associated with an increased risk for breast cancer

A 
ATM 
CHEK2 
PTEN 
PALB2
STK11
CDH1
NF1
TP53)

[¼ mark for NBN, RAD51C, RAD51D, FANCC, BARD1 – because the evidence is more limited but these later are found on breast cancer panels]

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11
Q

Reference: Genetics residents in-training examination – Fall 2020

A 26 year old woman presented with bilateral breast cancer and underwent genetic testing with a cancer gene panel that included all of the hereditary breast cancer genes. She was found to have a pathogenic variant in the TP53 gene. Her four-year-old son was then tested and found to have inherited the same pathogenic TP53 variant.

List three cancer surveillance recommendations you would advise for the son and what you are looking for?

A
  1. Ultrasound of abdomen and pelvis - adrenocortical carcinoma
    - every 3-4 months (not necessary to include frequency)
  2. Brain MRI - brain tumor
    - annually
  3. Whole-body MRI - soft-tissue and bone sarcoma
    - annually
  4. Complete physical - looking for signs of adrenocortical tumor or brain tumor – elevated blood pressure, accelerated growth, cushingoid features, signs of virilization, abnormal neurologic assessment
    - every 3-4 months
  5. Blood test for ACC hormones every 3-4 months (this is suggested only when abnormal findings on US).
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National In-training Exams (39 decks)

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