Incidence and clinical relevance of RET proto-oncogene germline mutations in pheochromocytoma patients
| Autor: | Andrzej Januszewicz, T. W. Apel, Włodzimierz Januszewicz, C. Szmigielski, Bożenna Wocial, Marek Kabat, B. Symonides, Lapiński M, I. Lon, Hartmut P. H. Neumann |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Nephrology medicine.medical_specialty Ambulatory blood pressure endocrine system diseases Physiology Adrenal Gland Neoplasms Pheochromocytoma RET proto-oncogene Proto-Oncogene Mas Gastroenterology Germline mutation Carcinoembryonic antigen Gene Frequency Proto-Oncogene Proteins Internal medicine Internal Medicine medicine Drosophila Proteins Humans Multiple endocrine neoplasia Germ-Line Mutation biology business.industry Proto-Oncogene Proteins c-ret Receptor Protein-Tyrosine Kinases Blood Pressure Monitoring Ambulatory medicine.disease Pedigree Endocrinology Blood pressure Parathyroid Hormone biology.protein Female Pentagastrin Poland Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Hypertension. 18:1019-1023 |
| ISSN: | 0263-6352 |
| DOI: | 10.1097/00004872-200018080-00005 |
| Popis: | Background Autosomal dominant cancer syndrome--multiple endocrine neoplasia type 2 (MEN 2), may exist more often than expected in patients with pheochromocytoma. Germline mutations identified recently in MEN 2 can be revealed by genetic screening. Objective To evaluate the frequency of RET (rearranged during transfection) mutations in patients with pheochromocytoma. Design and methods We genetically screened germline mutations in the RET proto-oncogene and clinically re-evaluated patients with pheochromocytoma. A pentagastrin test and other biochemical studies were performed in all patients. Setting Department of Internal Medicine and Hypertension, The Medical University of Warsaw, Warsaw, Poland and the Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany. Participants Seventy seven unselected patients with pheochromocytoma (19 men, 58 women, mean age: 51.55 +/- 1.5 years; pheochromocytoma confirmed histopathologically) out of 162 diagnosed and treated in the years 1957-1998 in the Department of Internal Medicine and Hypertension in Warsaw, Poland. The other 85 patients did not respond to the written invitation. Main outcome measures The finding of RET mutations and diagnosis of MEN 2 in patients with pheochromocytoma. Results Genetic testing revealed germline mutations in the RET proto-oncogene in six patients (7.8%). All carriers had mutation of exon 11, codon 634: TGC to CGC. In four patients with this mutation, medullary thyroid carcinoma (MIC) was diagnosed and in three cases, surgically treated. Biochemical parameters: parathormone 31.88 +/- 2.87 pg/ml, calcitonin: 0 min 0.23 +/- 0.14 ng/ml; 2 min 0.49 +/- 0.21 ng/ml; 5 min 0.48 +/- 0.21 ng/ml, metoxycatecholamines: 601.62 +/- 42.71 microg/24h, epinephrine: 1.94 +/- 0.17 microg/24h, norepinephrine 13.96 +/- 1.3 microg/24h, carcinoembryonic antigen (CEA) 9.94 +/- 4.3 ng/ml. Ambulatory blood pressure monitoring (ABPM): systolic blood pressure (SBP): 116 +/- 1.9 mmHg, diastolic blood pressure (DBP): 73.7 +/- 0.9 mmHg. Clinical, biochemical and imaging procedures did not reveal any recurrence of pheochromocytoma in the 77 patients studied. Conclusions Patients with pheochromocytoma should be genetically screened for mutations of the RET proto-oncogene. These patients should undergo clinical screening for MEN 2. In addition, genetic studies can be useful for the screening of the families of the carriers. |
| Databáze: | OpenAIRE |
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