| Title: |
Risk profile of the RET A883F germline mutation:an international collaborative study |
| Authors: |
Mathiesen, Jes Sloth; Habra, Mouhammed Amir; Bassett, John Howard Duncan; Choudhury, Sirazum Mubin; Balasubramanian, Sabapathy Prakash; Howlett, Trevor A; Robinson, Bruce G; Gimenez-Roqueplo, Anne-Paule; Castinetti, Frederic; Vestergaard, Peter; Frank-Raue, Karin |
| Source: |
Mathiesen, J S, Habra, M A, Bassett, J H D, Choudhury, S M, Balasubramanian, S P, Howlett, T A, Robinson, B G, Gimenez-Roqueplo, A-P, Castinetti, F, Vestergaard, P & Frank-Raue, K 2017, 'Risk profile of the RET A883F germline mutation : an international collaborative study', The Journal of Clinical Endocrinology & Metabolism, vol. 102, no. 6, pp. 2069-2074. https://doi.org/10.1210/jc.2016-3640 |
| Publication Year: |
2017 |
| Collection: |
University of Southern Denmark: Research Output / Syddansk Universitet |
| Subject Terms: |
Adolescent; Adrenal Gland Neoplasms/etiology; Adult; Carcinoma; Neuroendocrine/etiology; Child; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Male; Multiple Endocrine Neoplasia Type 2b/complications; Mutation; Penetrance; Pheochromocytoma/etiology; Proto-Oncogene Proteins c-ret/genetics; Retrospective Studies; Risk Assessment; Survival Rate; Thyroid Neoplasms/etiology; Thyroidectomy; Young Adult |
| Description: |
Context: The A883F germline mutation of the rearranged during transfection (RET) proto-oncogene causes multiple endocrine neoplasia 2B. In the revised American Thyroid Association (ATA) guidelines for the management of medullary thyroid carcinoma (MTC), the A883F mutation has been reclassified from the highest to the high-risk level, although no well-defined risk profile for this mutation exists. Objective: To create a risk profile for the A883F mutation for appropriate classification among the ATA risk levels. Design: Retrospective analysis. Setting: International collaboration. Patients: Included were 13 A883F carriers. Intervention: The intervention was thyroidectomy. Main Outcome Measures: Earliest age of MTC, regional lymph node metastases, distant metastases, age-related penetrance of MTC and pheochromocytoma (PHEO), overall and disease-specific survival, and biochemical cure rate. Results: One and three carriers were diagnosed at age 7 to 9 years (median, 7.5 years) with a normal thyroid and C-cell hyperplasia, respectively. Nine carriers were diagnosed with MTC at age 10 to 39 years (median, 19 years). The earliest age of MTC, regional lymph node metastasis, and distant metastasis was 10, 20, and 20 years, respectively. Fifty percent penetrance of MTC and PHEO was achieved by age 19 and 34 years, respectively. Five-and 10-year survival rates (both overall and disease specific) were 88% and 88%, respectively. Biochemical cure for MTC at latest follow-up was achieved in 63% (five of eight carriers) with pertinent data. Conclusions: MTC of A883F carriers seems to have a more indolent natural course compared with that of M918T carriers. Our results support the classification of the A883F mutation in the ATA highrisk level. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0021-972X; 1945-7197 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/28323957; info:eu-repo/semantics/altIdentifier/pissn/0021-972X; info:eu-repo/semantics/altIdentifier/eissn/1945-7197 |
| DOI: |
10.1210/jc.2016-3640 |
| Availability: |
https://portal.findresearcher.sdu.dk/da/publications/519c6445-2b98-45ee-95b0-1a14b9bb52b9; https://doi.org/10.1210/jc.2016-3640; https://findresearcher.sdu.dk/ws/files/125203071/Risk_profile_of_the_RET_A883F_germline_mutation.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.3E81ACF6 |
| Database: |
BASE |