TY - JOUR
T1 - The relationship between specific ret proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2
T2 - International RET mutation consortium analysis
AU - Eng, Charis
AU - Clayton, David
AU - Schuffenecker, Isabelle
AU - Lenoir, Gilbert
AU - Cote, Gilbert
AU - Gagel, Robert F.
AU - Ploos Van Amstel, Hans Kristian
AU - Lips, Cornelis J.M.
AU - Nishisho, Isamu
AU - Takai, Shin Ichiro
AU - Marsh, Debbie J.
AU - Robinson, Bruce G.
AU - Frank-Raue, Karin
AU - Raue, Friedhelm
AU - Xue, Feiyu
AU - Noll, Walter W.
AU - Romei, Cristina
AU - Pacini, Furio
AU - Fink, Monika
AU - Niederle, Bruno
AU - Zedenius, Jan
AU - Nordenskjöld, Magnus
AU - Komminoth, Paul
AU - Hendy, Geoffrey N.
AU - Gharib, Hossein
AU - Thibodeau, Stephen N.
AU - Lacroix, André
AU - Frilling, Andrea
AU - Ponder, Bruce A.J.
AU - Mulligan, Lois M.
PY - 1996/11/20
Y1 - 1996/11/20
N2 - Objective. - Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. Design. - Correlative survey study of 477 MEN 2 families. Setting. - Eighteen tertiary referral centers worldwide. Patients. - A total of 477 independent MEN 2 families. Main Outcome Measures. - Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. Results. - There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B- specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. Conclusions. - This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.
AB - Objective. - Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making. Design. - Correlative survey study of 477 MEN 2 families. Setting. - Eighteen tertiary referral centers worldwide. Patients. - A total of 477 independent MEN 2 families. Main Outcome Measures. - Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family. Results. - There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B- specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors. Conclusions. - This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.
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U2 - 10.1001/jama.276.19.1575
DO - 10.1001/jama.276.19.1575
M3 - Article
C2 - 8918855
AN - SCOPUS:4644256817
SN - 0098-7484
VL - 276
SP - 1575
EP - 1579
JO - JAMA
JF - JAMA
IS - 19
ER -