Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2

Anna Reimer Hansen; Line Borgwardt; Åse Krogh Rasmussen; Christian Godballe; Morten Møller Poulsen; Filipe G. Vieira; Jes Sloth Mathiesen; Maria Rossing

doi:10.3389/fendo.2021.764512

Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2

Anna Reimer Hansen, Line Borgwardt, Åse Krogh Rasmussen, Christian Godballe, Morten Møller Poulsen, Filipe G. Vieira, Jes Sloth Mathiesen, Maria Rossing^*

^*Corresponding author for this work

Department of Clinical Medicine - Department of Endocrinology and Internal Medicine

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Activating variants in the receptor tyrosine kinase REarranged during Transfection (RET) cause multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited cancer-susceptibility syndrome. The variant c.166C>A, p.Leu56Met in RET was recently reported in two patients with medullary thyroid cancer (MTC). The presence of a pheochromocytoma in one of the patients, suggested a possible pathogenic role of the variant in MEN 2A. Here, we present clinical follow up of a Danish RET Leu56Met cohort. Patients were evaluated for signs of MEN 2 according to a set of predefined criteria. None of the seven patients in our cohort exhibited evidence of MEN 2. Furthermore, we found the Leu56Met variant in our in-house diagnostic cohort with an allele frequency of 0.59%, suggesting that it is a common variant in the population. Additionally, none of the patients who harbored the allele were listed in the Danish MTC and MEN 2 registries. In conclusion, our findings do not support a pathogenic role of the Leu56Met variant in MEN 2.

Original language	English
Article number	764512
Journal	Frontiers in Endocrinology
Volume	12
ISSN	1664-2392
DOIs	https://doi.org/10.3389/fendo.2021.764512
Publication status	Published - Dec 2021

Keywords

Genetics
Leu56Met
medullary thyroid cancer
multiple endocrine neoplasia type 2
RET

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title = "Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2",

abstract = "Activating variants in the receptor tyrosine kinase REarranged during Transfection (RET) cause multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited cancer-susceptibility syndrome. The variant c.166C>A, p.Leu56Met in RET was recently reported in two patients with medullary thyroid cancer (MTC). The presence of a pheochromocytoma in one of the patients, suggested a possible pathogenic role of the variant in MEN 2A. Here, we present clinical follow up of a Danish RET Leu56Met cohort. Patients were evaluated for signs of MEN 2 according to a set of predefined criteria. None of the seven patients in our cohort exhibited evidence of MEN 2. Furthermore, we found the Leu56Met variant in our in-house diagnostic cohort with an allele frequency of 0.59%, suggesting that it is a common variant in the population. Additionally, none of the patients who harbored the allele were listed in the Danish MTC and MEN 2 registries. In conclusion, our findings do not support a pathogenic role of the Leu56Met variant in MEN 2.",

keywords = "Genetics, Leu56Met, medullary thyroid cancer, multiple endocrine neoplasia type 2, RET",

author = "Hansen, {Anna Reimer} and Line Borgwardt and Rasmussen, {{\AA}se Krogh} and Christian Godballe and Poulsen, {Morten M{\o}ller} and Vieira, {Filipe G.} and Mathiesen, {Jes Sloth} and Maria Rossing",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Hansen, Borgwardt, Rasmussen, Godballe, Poulsen, Vieira, Mathiesen and Rossing.",

year = "2021",

month = dec,

doi = "10.3389/fendo.2021.764512",

language = "English",

volume = "12",

journal = "Frontiers in Endocrinology",

issn = "1664-2392",

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Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2. / Hansen, Anna Reimer; Borgwardt, Line; Rasmussen, Åse Krogh et al.
In: Frontiers in Endocrinology, Vol. 12, 764512, 12.2021.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2

AU - Hansen, Anna Reimer

AU - Borgwardt, Line

AU - Rasmussen, Åse Krogh

AU - Godballe, Christian

AU - Poulsen, Morten Møller

AU - Vieira, Filipe G.

AU - Mathiesen, Jes Sloth

AU - Rossing, Maria

PY - 2021/12

Y1 - 2021/12

N2 - Activating variants in the receptor tyrosine kinase REarranged during Transfection (RET) cause multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited cancer-susceptibility syndrome. The variant c.166C>A, p.Leu56Met in RET was recently reported in two patients with medullary thyroid cancer (MTC). The presence of a pheochromocytoma in one of the patients, suggested a possible pathogenic role of the variant in MEN 2A. Here, we present clinical follow up of a Danish RET Leu56Met cohort. Patients were evaluated for signs of MEN 2 according to a set of predefined criteria. None of the seven patients in our cohort exhibited evidence of MEN 2. Furthermore, we found the Leu56Met variant in our in-house diagnostic cohort with an allele frequency of 0.59%, suggesting that it is a common variant in the population. Additionally, none of the patients who harbored the allele were listed in the Danish MTC and MEN 2 registries. In conclusion, our findings do not support a pathogenic role of the Leu56Met variant in MEN 2.

AB - Activating variants in the receptor tyrosine kinase REarranged during Transfection (RET) cause multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited cancer-susceptibility syndrome. The variant c.166C>A, p.Leu56Met in RET was recently reported in two patients with medullary thyroid cancer (MTC). The presence of a pheochromocytoma in one of the patients, suggested a possible pathogenic role of the variant in MEN 2A. Here, we present clinical follow up of a Danish RET Leu56Met cohort. Patients were evaluated for signs of MEN 2 according to a set of predefined criteria. None of the seven patients in our cohort exhibited evidence of MEN 2. Furthermore, we found the Leu56Met variant in our in-house diagnostic cohort with an allele frequency of 0.59%, suggesting that it is a common variant in the population. Additionally, none of the patients who harbored the allele were listed in the Danish MTC and MEN 2 registries. In conclusion, our findings do not support a pathogenic role of the Leu56Met variant in MEN 2.

KW - Genetics

KW - Leu56Met

KW - medullary thyroid cancer

KW - multiple endocrine neoplasia type 2

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JO - Frontiers in Endocrinology

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Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2

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