FP14-3 Multiple Endocrine Neoplasia Type 2A Due to An Exon 8 (G533C) Mutation in a Large Kindred in North America

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP14-Thyroid Cancer: Insights into Diagnosis & Treatment
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:10 AM
Room 103 (Moscone Center)

Poster Board SAT-416
M. Regina Castro*, Brittany Thomas, Melanie L. Richards, Jun Zhang and John C Morris
Mayo Clinic, Rochester, MN
Background:  Medullary thyroid cancer, although most commonly sporadic, may be part of MEN2 syndromes, which are generally due to mutations in the RET proto-oncogene. Most of these mutations are located in exons 10, 11, and 13-16, but occasionally, mutations in other exons have been described.  We report for the first time, a family from the United States with a rare mutation involving exon 8 of the RET proto-oncogene, corresponding to a Gly533Cys substitution (G533C) leading to the development of MEN2A syndrome in several affected family members.  This mutation had only been previously described in a large family in Brazil and in 7.75% of patients with apparently sporadic MTC in Greece.

Methods: Given strong index of suspicion in a patient with medullary thyroid cancer and strong family history, a genetic analysis was performed to evaluate for uncommon mutations in the RET proto-oncogene and identified the presence of the G533C missense mutation, despite initial negative screening for common mutations.  We describe a family with a total of 47 individuals from 5 generations with multiple members affected with this mutation.  

Results: Our data suggests that in patients with this mutation, pheochromocytoma is more common than previously reported and that in some cases this mutation may be associated with a more aggressive phenotype than initially described.   

Conclusions:  MEN2A due to G533C mutations in Exon 8 may be more common and more aggressive than previously recognized.  In patients with MTC with negative screening for common mutations in RET oncogene, but strong index of suspicion, DNA sequence analysis of less commonly involved  exons should be considered

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Nothing to Disclose: MRC, BT, MLR, JZ, JCM

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