Devita, Hellman, and Rosenberg's Cancer

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

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

Approximately two-thirds of all colon cancers in HNPCC occur in the

ascending colon. Consensus recommendations also include endometrial

cancer surveillance with transvaginal ultrasound and endometrial biopsy;

however, the efficacy of this screening regimen is unknown. Although

Diane’s (IV-1) paternal aunt (III-5) died of breast cancer at a young age,

there are insufficient data to prove breast cancer is one of the associ-

ated cancers in HNPCC syndrome. As such, intensified mammography

screening is not warranted. Intensified surveillance recommendations are

available for many hereditary cancer syndromes. Limited data exist to

prove the efficacy of these screening protocols. However, until larger data

sets are developed, consensus recommendations are issued to help guide

clinicians in the care of high-risk families.

Answer 14.4. The answer is C.

TheMSH2gene mutation, c.942+3A>T, identified in an affected

family member, results in an A>T change at the third nucleotide of the

splice-donor site of intron 5 and causes an in-frame deletion of exon 5.

The mutation can be detected using sequencing.

As such, site-specific sequencing, also known as targeted mutation

analysis, is the only test that is needed. Full sequencing of theMSH2

gene is unnecessary and may result in excess cost to the individual pur-

suing genetic testing. Approximately 20% ofMSH2 gene mutations

are large deletions or gene rearrangements. These mutations cannot be

detected using sequencing. Southern blot analysis and multiplex ligation-

dependent probe amplification are techniques used to detect large dele-

tions. A working knowledge of the types of mutations that have been

described for a given gene, as well as an understanding of the limitations

of the techniques used by a given laboratory, is crucial in overseeing the

clinical genetic testing of a family.

Diane (IV-1) has the right to pursue clinical genetic testing to aid in

her medical management. If her testing is positive for theMSH2gene

mutation, then her father and paternal grandmother may gain informa-

tion they have previously chosen not to obtain. In advance of ordering the

testing, it is crucial to discuss if and how Diane is going to communicate

her test results with her family and their potential reactions. By facilitating

this discussion, the clinician is acknowledging some of the psychosocial

implications associated with hereditary disease and providing anticipa-

tory guidance as to how Diane may address potential reactions from her

family.

Answer 14.5. The answer is D.

Several factors warrant genetic counseling for hereditary cancer syndrome

including young age at diagnosis, bilateral cancer in an affected family

member, and multiple affected generations.

Answer 14.6. The answer is E.

The family cancer history meets the diagnostic criteria for the heredi-

tary diffuse gastric cancer syndrome. HDGC is an autosomal-dominant,