Devita, Hellman, and Rosenberg's Cancer

LWBK1006-14 LWW-Govindan-Review November 24, 2011 11:28

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

Question 14.1. The family depicted has hereditary nonpolyposis colon cancer (HNPCC)

syndrome. This syndrome is characterized by a high risk to develop colon

and endometrial cancer and an increased risk to develop various other

tumor types. Before her death, individual III-2 had genetic testing of the

MLH1andMSH2genes, and anMSH2gene mutation was identified.

Specifically, the mutation is c.942+3A>T. MLH1, andMSH2gene

mutations account for 80% to 90% of families with HNPCC. Individual

II-1, depicted with the arrow, has not been diagnosed with cancer. He

has undergone frequent colonoscopy screening. He has also had genetic

testing and was found to carry the familyMSH2gene mutation. The

finding that individual II-1 has not been diagnosed with cancer can be

explained by which of the following concepts?

A. Genetic testing laboratory error

B. Clinical variability

C. Genetic heterogeneity

D. Reduced penetrance

Question 14.2. Assuming individual II-3 has the familyMSH2gene mutation, what is

the calculated probability Diane (individual IV-1) has inherited theMSH2

gene mutation?

A. 0%

B. 12.5%

C. 25%

D. 50%

Question 14.3. Diane (individual IV-1) is 24 years of age. She approaches her primary

care physician about her medical management, given her family history of

HNPCC syndrome. She has a healthy body weight and does not smoke.

Both her paternal grandmother (II-3) and her father (III-6) refuse to have

genetic testing. In addition to her annual PAP smear, which of the follow-

ing cancer screening is most appropriate for Diane?

A. Colonoscopy screening to begin at 50 years of age

B. Sigmoidoscopy screening to begin by 25 years of age

C. Colonoscopy screening to begin by 25 years of age

D. Colonoscopy and mammography screening to begin by 25 years of

age

Question 14.4. Diane (individual IV-1) decides to pursue genetic testing to aid in her

medical management. She states that her father will not undergo genetic

testing. What specific genetic test should be ordered?

A. Full sequencing of theMSH2gene

B. Full sequencing of theMSH2andMLH1genes

C. Site-specific targeted mutation analysis of theMSH2gene

D. Deletion analysis using multiplex ligation-dependent probe amplifi-

cation