Modifier Role of Common RET Variants in Sporadic Medullary Thyroid Carcinoma

Background: Although the disease-causing effect of pathogenic variants in the gene RET has been unambiguously identified, there is a lack of consensus regarding the possible impact of common variants in this gene. Our study aimed to test whether variants in exon...

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Autores principales:	Anna Skalniak, Małgorzata Trofimiuk-Müldner, Elwira Przybylik-Mazurek, Alicja Hubalewska-Dydejczyk
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	medullary thyroid carcinoma <i>RET</i> variants modifier Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c8186b6c07df4b18aba3ea38d0091e8a
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spelling	oai:doaj.org-article:c8186b6c07df4b18aba3ea38d0091e8a2021-11-11T17:14:33ZModifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma10.3390/ijms2221117941422-00671661-6596https://doaj.org/article/c8186b6c07df4b18aba3ea38d0091e8a2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11794https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<b>Background:</b> Although the disease-causing effect of pathogenic variants in the gene <i>RET</i> has been unambiguously identified, there is a lack of consensus regarding the possible impact of common variants in this gene. Our study aimed to test whether variants in exons 10, 11, and 13–16 that are commonly detected during routine diagnostic testing might have any modifying effect on MTC. <b>Methods:</b> In sporadic MTC patients with no pathogenic variants but with or without common variants in <i>RET</i>, the following variants were evaluated: rs1799939 (p.G691S), rs1800861 (p.L769=), rs1800862 (p.S836=), rs2472737 in intron 14, and rs1800863 (p.S904=). <b>Results:</b> After Bonferroni correction, none of the variants were statistically significantly associated with disease outcome when analysed independently. The MTC group was divided into three genetically different clusters by unsupervised k-means clustering. Those clusters differed significantly in the age at diagnosis. A trend towards the association of given clusters with metabolic disorders and with remission state was identified. <b>Conclusions:</b> Although common variants in <i>RET</i> are not responsible for the risk of MTC, their analysis might turn out useful in the prediction of a patient’s clinical outcome. Importantly, this analysis would come with no additional cost in laboratories with a diagnostic procedure based on exon sequencing.Anna SkalniakMałgorzata Trofimiuk-MüldnerElwira Przybylik-MazurekAlicja Hubalewska-DydejczykMDPI AGarticlemedullary thyroid carcinoma<i>RET</i> variantsmodifierBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11794, p 11794 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	medullary thyroid carcinoma <i>RET</i> variants modifier Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	medullary thyroid carcinoma <i>RET</i> variants modifier Biology (General) QH301-705.5 Chemistry QD1-999 Anna Skalniak Małgorzata Trofimiuk-Müldner Elwira Przybylik-Mazurek Alicja Hubalewska-Dydejczyk Modifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma
description	<b>Background:</b> Although the disease-causing effect of pathogenic variants in the gene <i>RET</i> has been unambiguously identified, there is a lack of consensus regarding the possible impact of common variants in this gene. Our study aimed to test whether variants in exons 10, 11, and 13–16 that are commonly detected during routine diagnostic testing might have any modifying effect on MTC. <b>Methods:</b> In sporadic MTC patients with no pathogenic variants but with or without common variants in <i>RET</i>, the following variants were evaluated: rs1799939 (p.G691S), rs1800861 (p.L769=), rs1800862 (p.S836=), rs2472737 in intron 14, and rs1800863 (p.S904=). <b>Results:</b> After Bonferroni correction, none of the variants were statistically significantly associated with disease outcome when analysed independently. The MTC group was divided into three genetically different clusters by unsupervised k-means clustering. Those clusters differed significantly in the age at diagnosis. A trend towards the association of given clusters with metabolic disorders and with remission state was identified. <b>Conclusions:</b> Although common variants in <i>RET</i> are not responsible for the risk of MTC, their analysis might turn out useful in the prediction of a patient’s clinical outcome. Importantly, this analysis would come with no additional cost in laboratories with a diagnostic procedure based on exon sequencing.
format	article
author	Anna Skalniak Małgorzata Trofimiuk-Müldner Elwira Przybylik-Mazurek Alicja Hubalewska-Dydejczyk
author_facet	Anna Skalniak Małgorzata Trofimiuk-Müldner Elwira Przybylik-Mazurek Alicja Hubalewska-Dydejczyk
author_sort	Anna Skalniak
title	Modifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma
title_short	Modifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma
title_full	Modifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma
title_fullStr	Modifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma
title_full_unstemmed	Modifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma
title_sort	modifier role of common <i>ret</i> variants in sporadic medullary thyroid carcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c8186b6c07df4b18aba3ea38d0091e8a
work_keys_str_mv	AT annaskalniak modifierroleofcommoniretivariantsinsporadicmedullarythyroidcarcinoma AT małgorzatatrofimiukmuldner modifierroleofcommoniretivariantsinsporadicmedullarythyroidcarcinoma AT elwiraprzybylikmazurek modifierroleofcommoniretivariantsinsporadicmedullarythyroidcarcinoma AT alicjahubalewskadydejczyk modifierroleofcommoniretivariantsinsporadicmedullarythyroidcarcinoma
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Modifier Role of Common <i>RET</i> Variants in Sporadic Medullary Thyroid Carcinoma

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