Devita, Hellman, and Rosenberg's Cancer

LWBK1006-03 LWW-Govindan-Review November 24, 2011 11:19

46 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

Answer 3.12. The answer is A.

BRCA1 and BRCA2 proteins function in DNA damage repair. BRCA1

and BRCA2 proteins are recruited to the site of double-stranded DNA

breaks along with other proteins. These complexes function to repair the

double-stranded break, although the precise role of BRCA1 and BRCA2

in these complexes remains unclear. These proteins have no known role

in cell-cycle regulation, microtubule stabilization, or angiogenesis.

Answer 3.13. The answer is B.

BRCA1 mutation carriers typically develop high grade, ER negative, and

Her2/neu negative invasive ductal carcinoma of the breast. On the other

hand, tumors in BRCA2 mutation carriers typically show a wider spec-

trum of histological features.

Answer 3.14. The answer is D.

NF1 is inherited in an autosomal-dominant manner with a 100% pene-

trance for neurofibromas, resulting from mutations in theNF1gene. NF1

encodes the neurofibromin protein, a GTPase activating protein for the

Ras family of proteins. Over 70 different mutations in NF1 have been

reported, with 70% of these mutations resulting in a truncated neurofi-

bromin protein. Mutations inSPRED1gene can give rise to a NF1-like

phenotype. Patients with NF1 syndrome develop neurofibromas and have

an increased risk for glioblastomas, pheochromocytomas, and myeloid

leukemias. Caf ́e au lait spots are found in 100% of patients with NF1

syndrome and increase in size and frequency with age. Genetic testing is

available but typically does not impact clinical management because the

disorder is readily identified by phenotype.

Answer 3.15. The answer is D.

FAP is caused by germ line mutations in theAPCgene on chromosome

5q that are inherited in an autosomal-dominant fashion. The character-

istic feature of FAP syndrome is the presence of numerous adenomatous

polyps. Development of colon cancer by the age of 40 years is a certainty.

Patients with FAP also have an increased risk of desmoids tumors and

malignancies of the upper gastrointestinal tract. Prophylactic colectomy

is recommended in these individuals to reduce the risk of colon cancer.

Nonsteroidal anti-inflammatory drugs can reduce the size and number of

the polyps in patients with FAP through the inhibition of COX-2 pathway

but are not recommended in place of surgery to reduce the risk of colon

cancer.

Answer 3.16. The answer is C.

p53 protein is a labile DNA-binding transcription factor that is not

expressed at high levels during normal cellular homeostasis. In response

to cellular stress, including hypoxia and DNA damage, p53 protein is

stabilized and activates transcription of growth arrest genes that halt the

cell in G1. The G1 arrest halts the cell until damage can be repaired. If the