Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan
| Autor: | Ken Miyanaga, Akira Miyauchi, Shiro Shakutsui, Hiroyuki Oya, Masafumi Koga, Shinichi Egawa, Kenichi Inoue, Takao Obara, Yoshio Nomura, Hitoyasu Futami, Masatoshi Iihara, Osamu Ishida, Akira Yoshimura, Yumi Takiyama, Kayo Takasaki, Ken Yamaguchi, Takeshi Tsujino, Toshitaka Ohi, Soichi Mugiya, Shinji Ishizuka, Masako Kanbe, Hiroyuki Inoue, Fujio Zeze, Hiroyuki Takei, Shoshu Mitsuyama, Takahiro Okamoto, Yukie Saio |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty endocrine system diseases Genotype medicine.medical_treatment Oncogene RET Adrenal Gland Neoplasms Multiple endocrine neoplasia type 2 Multiple Endocrine Neoplasia Type 2a Pheochromocytoma RET proto-oncogene Gastroenterology Proto-Oncogene Mas Germline mutation Internal medicine Proto-Oncogene Proteins medicine Drosophila Proteins Humans Point Mutation Radiology Nuclear Medicine and imaging Thyroid Neoplasms Multiple endocrine neoplasia business.industry Hyperparathyroidism Proto-Oncogene Proteins c-ret Thyroidectomy Receptor Protein-Tyrosine Kinases General Medicine medicine.disease Endocrinology Phenotype Oncology Carcinoma Medullary Female business |
| Zdroj: | Japanese journal of clinical oncology. 28(10) |
| ISSN: | 0368-2811 |
| Popis: | BACKGROUND Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype. |
| Databáze: | OpenAIRE |
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