Lecture 35 - Autosomal Dominant Cancer Predisposition

Question 1

____-______ Syndrome results from an inherited predisposition to cancer due to an autosomally dominant inherited mutation of _____ (tumor suppressor responisble for activating apop). This syndrome can also more rarely result from a mutation in CHEK2. This syndrome presents with a wide variety of tumors that typically occur at a young age.

Answer 1

Li-Fraumeni Syndrome

p53

Question 2

Neurofibromatosis (NF1) is an autosomal dominant that presents with cognitive defects, benign lesions of the _____ (Lisch nodules), hyperpigmentation defects (___-___-___ macules), and large numbers of benign _____ Fibromatomas. In 3% of cases, malignancy can develop if the second copy of NF1 is inhibited/lost, and this presents as malignant peripheral ____ sheath tumors (MPNSTs). Keep in mind only about ___% of cases show a family history of this disease.

Answer 2

Iris

cafe-au-lait macules

Dermal Neurofibromatomas

Malignant Peripheral Nerve Sheath Tumors

Question 3

How does NF1 interact with Ras?

Answer 3

NF1 acts as a catalyst for Ras hydrolysis of GTP to GDP. Without this, activated Ras bound to GTP builds, and the effect is essentially the same as having a mutation in Ras that knocks out its hydrolysis activity.

Question 4

In Familial Polyposis Coli, the _____ gene is mutated and loses its ability to regulate ___-_____ (a transcription factor that drives proliferation).

Answer 4

APC gene

Beta-Catenin

Question 5

Hereditary Nonpolyposis Coli (HNPCC - aka Lynch Syndrome) arises from mutations in DNA ______ repair genes MSH2 and MLH1. The reason this mutation leads to colon cancer is because the ____ gene has a long poly-A stretch in the coding sequence, making it highly susceptible to _____.

Answer 5

Mismatch repair genes

APC

Mismatches

Question 6

Though about 90% of breast an ovarian cancers are sporadic, hereditary breast and ovarian cancers exist and about HALF of these cases involve mutations in ____1 or ____2. Keep in mind these genes are likely involved in homologous recombination but are NOT implicated in sporadic cancer. Also, ____2 is implicated in Fanconi’s anemia.

Answer 6

BRCA1

BRCA2

BRCA2