Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Sarka Dvorakova x
Clear All Modify Search
Free access

Ioana N Milos, Karin Frank-Raue, Nelson Wohllk, Ana Luiza Maia, Eduardo Pusiol, Attila Patocs, Mercedes Robledo, Josefina Biarnes, Marta Barontini, Thera P Links, Jan Willem de Groot, Sarka Dvorakova, Mariola Peczkowska, Lisa A Rybicki, Maren Sullivan, Friedhelm Raue, Ioana Zosin, Charis Eng and Hartmut P H Neumann

RET testing in multiple endocrine neoplasia type 2 for molecular diagnosis is the paradigm for the practice of clinical cancer genetics. However, precise data for distinct mutation-based risk profiles are not available. Here, we survey the clinical profile for one specific genotype as a model, TGC to TGG in codon 634 (C634W). By international efforts, we ascertained all available carriers of the RET C634W mutation. Age at diagnosis, penetrance, and clinical complications were analyzed for medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism (HPT), as well as overall survival. Our series comprises 92 carriers from 20 unrelated families worldwide. Sixty-eight subjects had MTC diagnosed at age 3–72 years (mean 29). Lymph node metastases were observed in 16 subjects aged 20–72 and distant metastases in 4 subjects aged 28–69. Forty-one subjects had pheochromocytoma detected at age 18–67 (mean 36). Amongst the 28 subjects with MTC and pheochromocytoma, six developed pheochromocytoma before MTC. Six subjects had HPT diagnosed at age 26–52 (mean 39). Eighteen subjects died; of the 16 with known causes of death, 8 died of pheochromocytoma and 4 of MTC. Penetrance for MTC is 52% by age 30 and 83% by age 50, for pheochromocytoma penetrance is 20% by age 30 and 67% by age 50, and for HPT penetrance is 3% by age 30 and 21% by age 50. These data provide, for the first time, RET C634W-specific neoplastic risk and age-related penetrance profiles. The data may facilitate risk assessment and genetic counseling.

Free access

Frederic Castinetti, Ana Luiza Maia, Mariola Peczkowska, Marta Barontini, Kornelia Hasse-Lazar, Thera P Links, Rodrigo A Toledo, Sarka Dvorakova, Caterina Mian, Maria Joao Bugalho, Stefania Zovato, Maria Alevizaki, Andrei Kvachenyuk, Birke Bausch, Paola Loli, Simona R Bergmann, Attila Patocs, Marija Pfeifer, Josefina Biarnes Costa, Ernst von Dobschuetz, Claudio Letizia, Gerlof Valk, Marcin Barczynski, Malgorzata Czetwertynska, John T M Plukker, Paola Sartorato, Tomas Zelinka, Petr Vlcek, Svetlana Yaremchuk, Georges Weryha, Letizia Canu, Nelson Wohllk, Frederic Sebag, Martin K Walz, Charis Eng and Hartmut P H Neumann