TY - JOUR
T1 - Clinical characteristics of pheochromocytoma patients with germline mutations in SDHD
AU - Dannenberg, Hilde
AU - van Nederveen, Francien H.
AU - Abbou, Mustaffa
AU - Verhofstad, Albert A.
AU - Komminoth, Paul
AU - de Krijger, Ronald R.
AU - Dinjens, Winand N.M.
PY - 2005
Y1 - 2005
N2 - Purpose: We examined the value of SDHD mutation screening in patients presenting with apparently sporadic and familial pheochromocytoma for the identification of SDHD-related pheochromocytomas. Patients and Methods: This retrospective study involved 126 patients with adrenal or extra-adrenal pheochromocytomas, including 24 patients with a family history of multiple endocrine neoplasia 2, von Hippel-Lindau disease, neurofibromatosis type 1, or paraganglioma (PGL). Conformation-dependent gel electrophoresis and sequence determination analysis of germline and tumor DNA were used to identify SDHD alterations. The clinical and molecular characteristics of sporadic and hereditary tumors were compared. We reviewed the literature and compared our results with those from previously published studies. Results: Pathogenic germline SDHD mutations were identified in three patients: two (2.0%) of the 102 apparently sporadic pheochromocytoma patients and one patient with a family history of PGL. These patients presented with multifocal disease (two of three multifocal patients) or with a single adrenal tumor (one of 82 patients). In the literature, mutations are mostly found in patients ≤ 35 years of age or presenting with multifocal or extra-adrenal disease. All patients with an SDHD mutation developed extra-adrenal tumors (pheochromocytomas or PGLs) at presentation or during follow-up. Conclusion: SDHD gene mutations in patients presenting with apparently sporadic adrenal pheochromocytoma are rare. We recommend SDHD mutation screening for patients presenting with a family history of pheochromocytoma or PGL, multiple tumors, isolated adrenal or extraadrenal pheochromocytomas, and age ≤ 35 years. Analysis of SDHD can also help to distinguish synchronous primary tumors from abdominal metastases.
AB - Purpose: We examined the value of SDHD mutation screening in patients presenting with apparently sporadic and familial pheochromocytoma for the identification of SDHD-related pheochromocytomas. Patients and Methods: This retrospective study involved 126 patients with adrenal or extra-adrenal pheochromocytomas, including 24 patients with a family history of multiple endocrine neoplasia 2, von Hippel-Lindau disease, neurofibromatosis type 1, or paraganglioma (PGL). Conformation-dependent gel electrophoresis and sequence determination analysis of germline and tumor DNA were used to identify SDHD alterations. The clinical and molecular characteristics of sporadic and hereditary tumors were compared. We reviewed the literature and compared our results with those from previously published studies. Results: Pathogenic germline SDHD mutations were identified in three patients: two (2.0%) of the 102 apparently sporadic pheochromocytoma patients and one patient with a family history of PGL. These patients presented with multifocal disease (two of three multifocal patients) or with a single adrenal tumor (one of 82 patients). In the literature, mutations are mostly found in patients ≤ 35 years of age or presenting with multifocal or extra-adrenal disease. All patients with an SDHD mutation developed extra-adrenal tumors (pheochromocytomas or PGLs) at presentation or during follow-up. Conclusion: SDHD gene mutations in patients presenting with apparently sporadic adrenal pheochromocytoma are rare. We recommend SDHD mutation screening for patients presenting with a family history of pheochromocytoma or PGL, multiple tumors, isolated adrenal or extraadrenal pheochromocytomas, and age ≤ 35 years. Analysis of SDHD can also help to distinguish synchronous primary tumors from abdominal metastases.
UR - http://www.scopus.com/inward/record.url?scp=15744369194&partnerID=8YFLogxK
U2 - 10.1200/JCO.2005.07.198
DO - 10.1200/JCO.2005.07.198
M3 - Article
C2 - 15774781
AN - SCOPUS:15744369194
SN - 0732-183X
VL - 23
SP - 1894
EP - 1901
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -