Cancer Genetics II (will merge into cancer genetics eventually)

Question 1

CMMRD

Answer 1

• Constitutional Mismatch Repair Deficiency (CMMRD) (aka Biallelic Mismatch Repair Deficiency or Homozygous Mismatch Repair Mutations)
• AR
• Two mutations in Lynch syndrome genes (PMS2, MLH1, MSH1, MSH6)
• Derm signs like CALMs, axillary freckling
• VERY rare (only 200 cases)

Question 2

Tyrer-Cuzick

Answer 2

• FHx of br, ov, and/or Phx ov
• Can use with affected patient; caveat: only incorporates past hx of ovarian cancer into calc.; not appropriate in patients w/ breast cancer
• > 20% lifetime risk to increase MRI screening
• Only model to incorporate BRCA1/2 mutation status

Question 3

Claus

Answer 3

Good for:
-quick risk assessment for a woman with a very simple family history, which conveys a low prior probability but is of limited value in more complex or higher-risk situations

Cons:
-does not take into account more than two affected close relatives or information provided by unaffected relatives. So, if more than 2, the risk estimate will not go up

-results of mutation testing cannot be taken into account (because it was created before we knew about BRCA1/2)

Question 4

Gail

Answer 4

○ Only addresses Fhx br cancer in 1st degree relatives (or paternal); can’t use with affected patient
○ Used mostly in high risk clinics; for tamoxifen consideration; >1.7% threshold
○ Underestimates risk

Question 5

BRCAPro

Answer 5

• estimates risk of BRCA1/2 mutation
• Phx and Fam Hx of br, ov cancer
• takes into account a woman’s affected first- and second-degree relatives, as well as unaffected relatives

Question 6

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

Answer 6

• FH gene; AD
• cutaneous leiomyomata on trunk, extremities, face; uterine leiomyomata (fibroids); and/or renal tumors after age 25
• single aggressive kidney tumor @ median age of 44 in 1/3 of patients; 50% are metastatic. Most are papillary but can be tubulo-papillary renal cell carcinomas to collecting-duct renal cell carcinomas
• AR risk of Fumurase Hydratase Deficiency (an IEM)

Question 7

Birt Hogg Dube

Answer 7

FLCN; AD

• fibrofolliculomas (yellowish dome-shaped papules), trichodiscomas (multiple small papules), & acrochordons (skin tags) in 30s or 40s
• pulmonary cysts/history of pneumothorax
• various types of renal tumors (renal oncocytoma, chromophobe renal cell carcinoma, oncocytic hybrid tumor, and a minority of clear cell renal cell carcinoma) at median age of 48