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J Clin Endocrinol Metab. 2014 Jul;99(7):E1376-80. doi: 10.1210/jc.2013-3879. Epub 2014 Mar 31.

H-RAS mutations are restricted to sporadic pheochromocytomas lacking specific clinical or pathological features: data from a multi-institutional series.

Author information

1
Department of Pathology (L.O., R.R.d.K., W.N.M.D., E.K.), Erasmus MC University Medical Center, 3015 CN Rotterdam, The Netherlands; Department of Pathology (R.R.d.K.), Reinier de Graaf Hospital, 2625 AD Delft, The Netherlands; Department of Oncology (I.R., M.P., S.V., M.V.), University of Turin at San Luigi Hospital, 10043 Orbassano, Turin, Italy; Endocrine Research Unit (F.B), Medizinische Klinik und Poliklinik IV, Klinikum der Universit√§t M√ľnchen, D-81675 Munich, Germany; Hereditary Endocrine Cancer Group (A.A.d.C., V.M., M.R.), Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain; Department of Pathology and Molecular Genetics (A.P.D.T.), General Hospital, 31100 Treviso, Italy; Department of Clinical Pathophysiology (M.M.), University of Florence, 50121 Florence Italy; and Centre for Biomedical Network Research on Rare Diseases (CIBERER) (M.R.), 28029 Madrid, Spain.

Abstract

CONTEXT:

Somatic or germline mutations in up to 15 disease-causative genes are detectable in up to 50% of patients with pheochromocytoma (PCC) and paraganglioma (PGL). Very recently, somatic H-RAS mutations were identified by exome sequencing in approximately 7% in sporadic PCCs and PGLs, in association with male sex and benign behavior.

OBJECTIVE:

To explore the prevalence of RAS mutations in a cohort of 271 PCC and PGL from a European registry and to compare the genotype with clinical and pathological characteristics of potential clinical interest.

SETTING AND DESIGN:

Genetic screening for hotspot mutations in H-, N-, and K-RAS genes was performed by means of Sanger sequencing or pyrosequencing methods on tumor DNA in a series of patients with (n = 107) or without (n = 164) germline or somatic PCC/PGL-related gene mutations.

RESULTS:

Overall, H-RAS mutations were detected in 5.2% of cases (14/271), which were confined to sporadic PCCs resulting in a prevalence of 10% (14/140) in this cohort. In contrast, no mutations were found in PCC with PCC/PGL-related gene mutations (0/76) or in PGL (0/55) harboring or not mutations in PCC/PGL susceptibility genes. In this large series, H-RAS mutations in PCCs lacked any significant correlation with pathological or basic clinical endpoints.

CONCLUSIONS:

Somatic H-RAS mutations are restricted to a relevant proportion of sporadic PCC. These findings provide the basis to study potential H-RAS-dependent correlations with long-term outcome data.

PMID:
24684458
DOI:
10.1210/jc.2013-3879
[Indexed for MEDLINE]
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