Genetic Mutation Screening in an Italian Cohort of Nonsyndromic Pheochromocytoma/Paraganglioma Patients

• DOI: 10.1196/annals.1353.016
• Publication Date: 2006-11-14T00:28:06Z
• Authors: M. CASTELLANO; L. MORI; M. GIACCHÈ; E. AGLIOZZO; R. TOSINI; A. PANAROTTO; C. CAPPELLI; P. MULATERO; D. CUMETTI; F. VEGLIO; E. AGABITI‐ROSEI
• Keywords: Base Sequence; Sequence Homology, Amino Acid; Molecular Sequence Data; Proto-Oncogene Proteins c-ret; Adrenal Gland Neoplasms; Pheochromocytoma; 3. Good health; pheochromocytoma; genetics; Cohort Studies; Paraganglioma; Succinate Dehydrogenase; 03 medical and health sciences; 0302 clinical medicine; Italy; Von Hippel-Lindau Tumor Suppressor Protein; Mutation; pheocromocitoma; Humans; Amino Acid Sequence; DNA Primers

Abstract: To assess the prevalence of genetic mutations in nonsyndromic pheochromocytoma/paraganglioma (PHEO/PGL) patients we have performed a systematic search for succinate dehydrogenase (SDH) B, C, and D subunits, von Hippel–Lindau (VHL), RET genes by direct bidirectional sequencing. Patients were selected from medical records hypertension centers. After exclusion syndromic patients, 45 with familial (F+, n = 3) sporadic (F−, 42) cases isolated PHEO/PGL considered. They included 35 PHEO, 7 PGL, 3 head/neck PGL (hnPGL). Three PHEO (2F−, 1F+) presented VHL (P86A, G93C, R167W), six (4F−, 2F+) positive SDH or (SDHB R230G two SDHB S8F, R46Q, R90Q, P81L one subject each), hnPGL carried SDHD 348–351delGACT mutation. We also detected missense S163P, H50R G12S), synonymous A6A, S68S), intronic that been considered nonpathological polymorphic variants. No mutation was found SDHC genes. Our data indicate germline subunits are not infrequent as well (overall, 12 probands, 22%). Accordingly, screening such seems to be justified. However, more precise characterization functional relevance any observed sequence variant other environmental determinants neoplastic transformation is essential order plan appropriate protocols family follow‐up.