TY - JOUR
T1 - Genotype-Phenotype Correlation of Patients with Multiple Endocrine Neoplasia Type 2 in Japan
AU - Egawa, Shin Ichi
AU - Futami, Hitoyasu
AU - Takasaki, Kayo
AU - Iihara, Masatoshi
AU - Okamoto, Takahiro
AU - Kanbe, Masako
AU - Ohi, Toshitaka
AU - Saio, Yukie
AU - Miyauchi, Akira
AU - Takiyama, Yumi
AU - Koga, Masafumi
AU - Miyanaga, Ken
AU - Inoue, Ken Ichi
AU - Mitsuyama, Shoshu
AU - Nomura, Yoshio
AU - Takei, Hiroyuki
AU - Mugiya, Soichi
AU - Ishida, Osamu
AU - Zeze, Fujio
AU - Shakutsui, Shiro
AU - Inoue, Hiroyuki
AU - Oya, Hiroyuki
AU - Yoshimura, Akira
AU - Ishizuka, Shinji
AU - Tsujino, Takeshi
AU - Obara, Takao
AU - Yamaguchi, Ken
N1 - Funding Information:
The authors are indebted to the patients and families who participated in this study for their cooperation, to Dr Kiyomi Yamazaki of the Department of Endocrine Surgery, Tokyo Women's Medical College, for contributing the nationwide questionnaire survey, to Drs Koichi Nagasaki, Toshihiko Tsukada, Kazuki Sasaki and Kouji Maruyama of the Growth Factor Division, National Cancer Center Research Institute, for fruitful suggestions and to Ms Mon Ebinuma for her excellent technical assistance. This research was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for the Second-term Comprehensive 10-Year Strategy for Cancer Control and by Grants-in-Aid for Cancer Research (8-33 and 10-28) from the Ministry of Health and Welfare.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
KW - DNA testing
KW - Genotype-phenotype correlation
KW - Multiple endocrine neoplasia
KW - RET proto-oncogene
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U2 - 10.1093/jjco/28.10.590
DO - 10.1093/jjco/28.10.590
M3 - Article
C2 - 9839497
AN - SCOPUS:0032188092
SN - 0368-2811
VL - 28
SP - 590
EP - 596
JO - Japanese Journal of Clinical Oncology
JF - Japanese Journal of Clinical Oncology
IS - 10
ER -
