TY - JOUR

T1 - Long-term follow-up of RET Y791F carriers in Denmark 1994-2017

T2 - A National Cohort Study

AU - Høxbroe Michaelsen, Sanne

AU - Ornstrup, Marie Juul

AU - Poulsen, Morten Møller

AU - Bennedbæk, Finn Noe

AU - Gaustadnes, Mette

AU - Rossing, Maria

AU - Darling, Peter

AU - Vestergaard, Peter

AU - Mathiesen, Jes Sloth

PY - 2019

Y1 - 2019

N2 - BACKGROUND AND OBJECTIVES: Recently, a comprehensive study presented evidence that a long-disputed REarranged during Transfection (RET) variant, RET Y791F, should be classified as nonpathogenic. In spite of this, several subsequently published papers, including the revised American Thyroid Association guidelines for medullary thyroid carcinoma, refer to the variant as pathogenic. This study presents data from a unique national Danish cohort of RET Y791F carriers who have been followed by watchful waiting instead of being subjected to early thyroidectomy, to determine if any carrier shows evidence of multiple endocrine neoplasia 2A (MEN2A) at long-term follow-up.METHODS: A national cohort of all patients tested for RET mutations in Denmark from September 1994 to October 2017 was searched for carriers of RET Y791F. Medical records and laboratory reports of carriers were reviewed for signs of MEN2A at latest follow-up (medullary thyroid carcinoma, primary hyperparathyroidism, pheochromocytoma, cutaneous lichen amyloidosis, or Hirschsprung's disease).RESULTS: In total, twenty RET Y791F-carriers were identified, none of whom showed any evidence of MEN2A, despite an age range from 7 to 87 years.CONCLUSIONS: Our national cohort study of all Danish RET Y791F carriers substantiates the claim that the RET Y791F variant is nonpathogenic.

AB - BACKGROUND AND OBJECTIVES: Recently, a comprehensive study presented evidence that a long-disputed REarranged during Transfection (RET) variant, RET Y791F, should be classified as nonpathogenic. In spite of this, several subsequently published papers, including the revised American Thyroid Association guidelines for medullary thyroid carcinoma, refer to the variant as pathogenic. This study presents data from a unique national Danish cohort of RET Y791F carriers who have been followed by watchful waiting instead of being subjected to early thyroidectomy, to determine if any carrier shows evidence of multiple endocrine neoplasia 2A (MEN2A) at long-term follow-up.METHODS: A national cohort of all patients tested for RET mutations in Denmark from September 1994 to October 2017 was searched for carriers of RET Y791F. Medical records and laboratory reports of carriers were reviewed for signs of MEN2A at latest follow-up (medullary thyroid carcinoma, primary hyperparathyroidism, pheochromocytoma, cutaneous lichen amyloidosis, or Hirschsprung's disease).RESULTS: In total, twenty RET Y791F-carriers were identified, none of whom showed any evidence of MEN2A, despite an age range from 7 to 87 years.CONCLUSIONS: Our national cohort study of all Danish RET Y791F carriers substantiates the claim that the RET Y791F variant is nonpathogenic.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Carcinoma, Medullary/genetics

KW - Child

KW - Cohort Studies

KW - Denmark/epidemiology

KW - Follow-Up Studies

KW - Genetic Predisposition to Disease/epidemiology

KW - Heterozygote

KW - Humans

KW - Middle Aged

KW - Multiple Endocrine Neoplasia Type 2a/genetics

KW - Mutation

KW - Pheochromocytoma/genetics

KW - Proto-Oncogene Proteins c-ret/genetics

KW - Thyroid Neoplasms/genetics

KW - Young Adult

U2 - 10.1002/jso.25371

DO - 10.1002/jso.25371

M3 - Journal article

C2 - 30644554

VL - 119

SP - 687

EP - 693

JO - Journal of Surgical Oncology

JF - Journal of Surgical Oncology

SN - 0022-4790

IS - 6

ER -