Pheochromocytoma penetrance varies by RET mutation in MEN 2A

Frank J. Quayle, Elizabeth A. Fialkowski, Ronald Benveniste, Jeffrey F. Moley

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Abstract

Background: The occurrence of pheochromocytoma in multiple endocrine neoplasia type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC expression for specific MEN 2A RET mutations. Methods: Charts of MEN 2A patients enrolled in our multiple endocrine neoplasia program from 1990 to 2001 were reviewed retrospectively. Statistical analysis was performed using SAS software (SAS Institute, Inc, Cary, NC). Results: RET mutation data and pheochromocytoma data were compiled for 323 patients. Overall, penetrance of pheochromocytoma occurred in 102 of 323 patients (32%). Bilateral pheochromocytomas were observed in 67 patients (66%). The following codon-specific expression of pheochromocytoma was observed: 1 of 24 patients expressed codon 609 (4%), 0 of 5 patients expressed codon 611 (0%), 23 of 105 patients expressed codon 618 (22%), 4 of 45 patients expressed codon 620 (9%), and 74 of 149 patients expressed codon 634 (50%) (P < .001). An association between pheochromocytoma expression and amino acid substitutions at codon 618 was observed as follows: 0 of 7 patients with C618F, 5 of 21 patients with C618G (24%), 11 of 27 patients with C618R (41%), 7 of 41 patients with C618S (17%), and 0 of 9 patients with C618Y (P = .04.) In our cohort, no deaths were attributable to PC with a median follow-up of 9 years. Conclusions: The penetrance of PC varies between MEN 2A RET codon mutations. Furthermore, we observed variable expression with different amino acid substitutions at the same codon. These results may help guide screening and therapy for MEN 2A patients.

Original languageEnglish
Pages (from-to)800-805
Number of pages6
JournalSurgery
Volume142
Issue number6
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

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Multiple Endocrine Neoplasia Type 2a
Penetrance
Pheochromocytoma
Mutation
Codon
Amino Acid Substitution
Multiple Endocrine Neoplasia

ASJC Scopus subject areas

  • Surgery

Cite this

Pheochromocytoma penetrance varies by RET mutation in MEN 2A. / Quayle, Frank J.; Fialkowski, Elizabeth A.; Benveniste, Ronald; Moley, Jeffrey F.

In: Surgery, Vol. 142, No. 6, 01.12.2007, p. 800-805.

Research output: Contribution to journalArticle

Quayle, Frank J. ; Fialkowski, Elizabeth A. ; Benveniste, Ronald ; Moley, Jeffrey F. / Pheochromocytoma penetrance varies by RET mutation in MEN 2A. In: Surgery. 2007 ; Vol. 142, No. 6. pp. 800-805.
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abstract = "Background: The occurrence of pheochromocytoma in multiple endocrine neoplasia type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC expression for specific MEN 2A RET mutations. Methods: Charts of MEN 2A patients enrolled in our multiple endocrine neoplasia program from 1990 to 2001 were reviewed retrospectively. Statistical analysis was performed using SAS software (SAS Institute, Inc, Cary, NC). Results: RET mutation data and pheochromocytoma data were compiled for 323 patients. Overall, penetrance of pheochromocytoma occurred in 102 of 323 patients (32{\%}). Bilateral pheochromocytomas were observed in 67 patients (66{\%}). The following codon-specific expression of pheochromocytoma was observed: 1 of 24 patients expressed codon 609 (4{\%}), 0 of 5 patients expressed codon 611 (0{\%}), 23 of 105 patients expressed codon 618 (22{\%}), 4 of 45 patients expressed codon 620 (9{\%}), and 74 of 149 patients expressed codon 634 (50{\%}) (P < .001). An association between pheochromocytoma expression and amino acid substitutions at codon 618 was observed as follows: 0 of 7 patients with C618F, 5 of 21 patients with C618G (24{\%}), 11 of 27 patients with C618R (41{\%}), 7 of 41 patients with C618S (17{\%}), and 0 of 9 patients with C618Y (P = .04.) In our cohort, no deaths were attributable to PC with a median follow-up of 9 years. Conclusions: The penetrance of PC varies between MEN 2A RET codon mutations. Furthermore, we observed variable expression with different amino acid substitutions at the same codon. These results may help guide screening and therapy for MEN 2A patients.",
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