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Gene mutation may signal presence of adrenal tumors
Yao L. JAMA. 2010;304:2611-2619.
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Researchers have identified variations of a gene that are associated with the development of pheochromocytomas.
Between 2009 and 2010, researchers sequenced FP/TMEM127 — a gene recently characterized as susceptible to pheochromocytomas — in samples from 990 patients with pheochromocytomas, paragangliomas or both, including 898 previously unreported cases with no mutations in other susceptibility genes.
Forty-four variants of FP/TMEM127 were detected among all of the samples. Nineteen of these mutations, 13 of which were newly discovered, found in 20 patients were deemed as having potential pathogenic significance. Mutations were detected only in patients with tumors of adrenal localization, but not with paragangliomas.
The age group in which these variations were found is frequently excluded from genetic screening models for this type of tumor, according to the researchers. Onset of adrenal tumors associated with FP/TMEM127 mutations occurred at a mean age of 42.8 years (95% CI, 36.44-49.25). The age at onset was similar to the average of non-mutated cases in this series (43.2 years), and to the reported average diagnostic age for sporadic pheochromocytomas (47 years).
Almost all tumors were benign; one patient developed malignancy in the form of multiple vertebral metastases. Bilateral tumors and familial disease accounted for nearly half of the cases associated with FP/TMEM127 mutations, and one-third of patients had sporadic, benign pheochromocytomas appear after age 40 years.
No recurrent clinical manifestations were observed, but the appearance of other neoplasias in three patients led the researchers to conclude that “clinical disease associated with FP/TMEM127 mutations may mimic other pheochromocytoma-associated syndromes.”
Additionally, the expression of five novel FP/TMEM127 mutations indicated that, unlike wild-type TMEM127, the mutant proteins localized diffusely within the cytoplasm.
“The preliminary genotype-phenotype associations reported in the present study can be used to further refine genetic testing priorities in patients with pheochromocytomas and suggest that FP/TMEM127 mutation screening may be recommended for patients presenting at an older age with adrenal tumors, especially but not exclusively those with bilateral disease,” the researchers wrote.
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