Genetic testing for familial cancer. Consequences of RET proto-oncogene mutation analysis in multiple endocrine
D L Learoyd1, D J Marsh, A L Richardson
1Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia.
Objective:
To assess clinician use and acceptance of RET proto-oncogene mutation testing in multiple endocrine neoplasia, type 2 (MEN 2) family members.
Design:
A retrospective survey of clinicians managing 26 MEN 2 families with documented RET mutations to assess the effect of genetic screening on subsequent investigation and management of family members.
Setting:
Tertiary referral center for RET mutation testing.
Main Outcome Measures:
The screening procedures used by clinicians and the altered incidence of C-cell hyperplasia vs medullary thyroid carcinoma in genetically as opposed to biochemically identified affected family members.
Results:
Among RET mutation-positive patients, thyroidectomy performed for clinical or biochemical indication disclosed medullary thyroid carcinoma in 44 (98%) of 45 patients and precursor C-cell hyperplasia in only 1 (2%) patient. When prophylactic thyroidectomy was performed based on a positive genetic result, medullary thyroid carcinoma occurred in 3 (43%) of 7 patients and C-cell hyperplasia in 4 (57%) of 7 patients (P < .001). RET mutation-negative patients were not subjected to further biochemical testing, but 4 had already undergone thyroidectomy based on abnormal results of pentagastrin stimulation tests, including 2 patients who were known to be RET mutation-negative at the time of surgery. RET mutation testing was well accepted and resulted in additional family members consenting to screening in more than 85% of families.
Conclusions:
Genetic screening for RET proto-oncogene mutations in MEN 2 is a powerful diagnostic tool that enables prophylactic thyroidectomy to be performed in RET mutation-positive patients at an earlier stage of the disease process than does traditional biochemical screening.
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