CGC Cancer Genetics & Hereditary Syndromes 1 — Questions and Answers
Question 1: Which hereditary syndrome is associated with pathogenic variants in the BRCA1 and BRCA2 genes?
- Lynch syndrome
- Hereditary breast and ovarian cancer (HBOC) syndrome (Correct answer)
- Li-Fraumeni syndrome
- Cowden syndrome
Correct answer: Hereditary breast and ovarian cancer (HBOC) syndrome
BRCA1 and BRCA2 pathogenic variants are the hallmark of hereditary breast and ovarian cancer (HBOC) syndrome.
Question 2: Lynch syndrome is caused by pathogenic variants in which set of genes?
- BRCA1, BRCA2, PALB2
- MLH1, MSH2, MSH6, PMS2, EPCAM (Correct answer)
- APC, MUTYH, NTHL1
- TP53, CHEK2, ATM
Correct answer: MLH1, MSH2, MSH6, PMS2, EPCAM
Lynch syndrome results from germline pathogenic variants in mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2, and EPCAM (which silences MSH2).
Question 3: A patient has a personal history of colorectal cancer at age 38 with MSI-high tumor testing. This MOST likely suggests:
- Familial adenomatous polyposis (FAP)
- Lynch syndrome (Correct answer)
- MUTYH-associated polyposis (MAP)
- Serrated polyposis syndrome
Correct answer: Lynch syndrome
Early-onset colorectal cancer with MSI-high tumor testing is a classic presentation prompting evaluation for Lynch syndrome.
Question 4: The Amsterdam II criteria are used to identify families at high risk for:
- HBOC syndrome
- Li-Fraumeni syndrome
- Lynch syndrome (Correct answer)
- Familial adenomatous polyposis
Correct answer: Lynch syndrome
The Amsterdam II criteria identify families with increased risk for Lynch syndrome based on colorectal cancer and Lynch-spectrum cancers across generations.
Question 5: A patient with Li-Fraumeni syndrome carries a germline TP53 pathogenic variant. Which of the following cancer surveillance recommendations is MOST appropriate?
- Annual mammography starting at age 40 only
- Whole-body MRI annually, with brain MRI and breast MRI included (Correct answer)
- Colonoscopy every 3 years starting at age 25
- No surveillance needed until symptoms arise
Correct answer: Whole-body MRI annually, with brain MRI and breast MRI included
Whole-body MRI is the primary surveillance tool for Li-Fraumeni syndrome due to the broad spectrum of associated cancers.
Question 6: Which of the following is a characteristic feature of hereditary diffuse gastric cancer (HDGC) syndrome?
- Pathogenic variants in SMAD4
- Germline CDH1 pathogenic variants and lobular breast cancer risk (Correct answer)
- Multiple colonic polyps
- Hamartomatous polyps of the GI tract
Correct answer: Germline CDH1 pathogenic variants and lobular breast cancer risk
HDGC is caused by CDH1 germline pathogenic variants and confers high risks for diffuse gastric cancer and lobular breast cancer.
CGC Cancer Genetics & Hereditary Syndromes 1
Which hereditary syndrome is associated with pathogenic variants in the BRCA1 and BRCA2 genes?