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Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value
Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine tumour whose diagnosis includes evaluating calcitonin serum levels, which can present fluctuations unrelated to MTC. Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free...
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Published in: | Biomarker research 2023-09, Vol.11 (1), p.1-82, Article 82 |
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creator | Citarella, Anna Besharat, Zein Mersini Trocchianesi, Sofia Autilio, Tanja Milena Verrienti, Antonella Catanzaro, Giuseppina Splendiani, Elena Spinello, Zaira Cantara, Silvia Zavattari, Patrizia Loi, Eleonora Romei, Cristina Ciampi, Raffaele Pezzullo, Luciano Castagna, Maria Grazia Angeloni, Antonio Elisei, Rosella Durante, Cosimo Po, Agnese Ferretti, Elisabetta |
description | Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine tumour whose diagnosis includes evaluating calcitonin serum levels, which can present fluctuations unrelated to MTC. Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free DNA (cfDNA) isolated from the plasma of MTC patients. For cfDNA fragmentation analysis, we investigated the fragment size distribution of a gene family and calculated short fragment fraction (SFF). Methylation analyses evaluated the methylation levels of CG_16698623, a CG dinucleotide in the MGMT gene that we found hypermethylated in MTC tissues by analyzing public databases. The SFF ratio and methylation of CG_16698623 were significantly increased in plasma from MTC patients at diagnosis, and patients with clinical remission or stable disease at follow-up showed no significant SFF difference compared with healthy subjects. Our data support the diagnostic value of cfDNA traits that could enable better management of MTC patients. |
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Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free DNA (cfDNA) isolated from the plasma of MTC patients. For cfDNA fragmentation analysis, we investigated the fragment size distribution of a gene family and calculated short fragment fraction (SFF). Methylation analyses evaluated the methylation levels of CG_16698623, a CG dinucleotide in the MGMT gene that we found hypermethylated in MTC tissues by analyzing public databases. The SFF ratio and methylation of CG_16698623 were significantly increased in plasma from MTC patients at diagnosis, and patients with clinical remission or stable disease at follow-up showed no significant SFF difference compared with healthy subjects. Our data support the diagnostic value of cfDNA traits that could enable better management of MTC patients.</description><identifier>ISSN: 2050-7771</identifier><identifier>EISSN: 2050-7771</identifier><identifier>DOI: 10.1186/s40364-023-00522-4</identifier><identifier>PMID: 37726827</identifier><language>eng</language><publisher>London: BioMed Central Ltd</publisher><subject>Analysis ; Biomarkers ; Calcitonin ; Cancer ; Carcinoma ; Cell-free DNA ; Circulating biomarker ; Circulating DNA fragmentation ; Circulating DNA methylation ; Correspondence ; Diagnosis ; DNA ; DNA fragmentation ; DNA methylation ; Epigenetics ; Genetic aspects ; Internet ; Medullary thyroid carcinoma ; Methylation ; Mutation ; Neuroendocrine tumors ; Rare tumour ; Remission ; Serum levels ; Size distribution ; Surgery ; Thyroid cancer ; Thyroid carcinoma ; Thyroid diseases ; Trends ; Tumors</subject><ispartof>Biomarker research, 2023-09, Vol.11 (1), p.1-82, Article 82</ispartof><rights>COPYRIGHT 2023 BioMed Central Ltd.</rights><rights>2023. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Yumed Inc. and BioMed Central Ltd., part of Springer Nature 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c526t-7e39dd3d0add0316cc4337bef878719643c2437a55dd19628815fbe0054caf523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510276/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2877495081?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids></links><search><creatorcontrib>Citarella, Anna</creatorcontrib><creatorcontrib>Besharat, Zein Mersini</creatorcontrib><creatorcontrib>Trocchianesi, Sofia</creatorcontrib><creatorcontrib>Autilio, Tanja Milena</creatorcontrib><creatorcontrib>Verrienti, Antonella</creatorcontrib><creatorcontrib>Catanzaro, Giuseppina</creatorcontrib><creatorcontrib>Splendiani, Elena</creatorcontrib><creatorcontrib>Spinello, Zaira</creatorcontrib><creatorcontrib>Cantara, Silvia</creatorcontrib><creatorcontrib>Zavattari, Patrizia</creatorcontrib><creatorcontrib>Loi, Eleonora</creatorcontrib><creatorcontrib>Romei, Cristina</creatorcontrib><creatorcontrib>Ciampi, Raffaele</creatorcontrib><creatorcontrib>Pezzullo, Luciano</creatorcontrib><creatorcontrib>Castagna, Maria Grazia</creatorcontrib><creatorcontrib>Angeloni, Antonio</creatorcontrib><creatorcontrib>Elisei, Rosella</creatorcontrib><creatorcontrib>Durante, Cosimo</creatorcontrib><creatorcontrib>Po, Agnese</creatorcontrib><creatorcontrib>Ferretti, Elisabetta</creatorcontrib><title>Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value</title><title>Biomarker research</title><description>Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine tumour whose diagnosis includes evaluating calcitonin serum levels, which can present fluctuations unrelated to MTC. Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free DNA (cfDNA) isolated from the plasma of MTC patients. For cfDNA fragmentation analysis, we investigated the fragment size distribution of a gene family and calculated short fragment fraction (SFF). Methylation analyses evaluated the methylation levels of CG_16698623, a CG dinucleotide in the MGMT gene that we found hypermethylated in MTC tissues by analyzing public databases. The SFF ratio and methylation of CG_16698623 were significantly increased in plasma from MTC patients at diagnosis, and patients with clinical remission or stable disease at follow-up showed no significant SFF difference compared with healthy subjects. Our data support the diagnostic value of cfDNA traits that could enable better management of MTC patients.</description><subject>Analysis</subject><subject>Biomarkers</subject><subject>Calcitonin</subject><subject>Cancer</subject><subject>Carcinoma</subject><subject>Cell-free DNA</subject><subject>Circulating biomarker</subject><subject>Circulating DNA fragmentation</subject><subject>Circulating DNA methylation</subject><subject>Correspondence</subject><subject>Diagnosis</subject><subject>DNA</subject><subject>DNA fragmentation</subject><subject>DNA methylation</subject><subject>Epigenetics</subject><subject>Genetic aspects</subject><subject>Internet</subject><subject>Medullary thyroid carcinoma</subject><subject>Methylation</subject><subject>Mutation</subject><subject>Neuroendocrine tumors</subject><subject>Rare tumour</subject><subject>Remission</subject><subject>Serum levels</subject><subject>Size distribution</subject><subject>Surgery</subject><subject>Thyroid cancer</subject><subject>Thyroid carcinoma</subject><subject>Thyroid 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Romei, Cristina ; Ciampi, Raffaele ; Pezzullo, Luciano ; Castagna, Maria Grazia ; Angeloni, Antonio ; Elisei, Rosella ; Durante, Cosimo ; Po, Agnese ; Ferretti, Elisabetta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-7e39dd3d0add0316cc4337bef878719643c2437a55dd19628815fbe0054caf523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Biomarkers</topic><topic>Calcitonin</topic><topic>Cancer</topic><topic>Carcinoma</topic><topic>Cell-free DNA</topic><topic>Circulating biomarker</topic><topic>Circulating DNA fragmentation</topic><topic>Circulating DNA methylation</topic><topic>Correspondence</topic><topic>Diagnosis</topic><topic>DNA</topic><topic>DNA fragmentation</topic><topic>DNA methylation</topic><topic>Epigenetics</topic><topic>Genetic aspects</topic><topic>Internet</topic><topic>Medullary thyroid 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Anna</au><au>Besharat, Zein Mersini</au><au>Trocchianesi, Sofia</au><au>Autilio, Tanja Milena</au><au>Verrienti, Antonella</au><au>Catanzaro, Giuseppina</au><au>Splendiani, Elena</au><au>Spinello, Zaira</au><au>Cantara, Silvia</au><au>Zavattari, Patrizia</au><au>Loi, Eleonora</au><au>Romei, Cristina</au><au>Ciampi, Raffaele</au><au>Pezzullo, Luciano</au><au>Castagna, Maria Grazia</au><au>Angeloni, Antonio</au><au>Elisei, Rosella</au><au>Durante, Cosimo</au><au>Po, Agnese</au><au>Ferretti, Elisabetta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value</atitle><jtitle>Biomarker research</jtitle><date>2023-09-19</date><risdate>2023</risdate><volume>11</volume><issue>1</issue><spage>1</spage><epage>82</epage><pages>1-82</pages><artnum>82</artnum><issn>2050-7771</issn><eissn>2050-7771</eissn><abstract>Medullary Thyroid Carcinoma (MTC) is a rare neuroendocrine tumour whose diagnosis includes evaluating calcitonin serum levels, which can present fluctuations unrelated to MTC. Here, we investigated circulating DNA fragmentation and methylation changes as potential biomarkers using ddPCR on cell-free DNA (cfDNA) isolated from the plasma of MTC patients. For cfDNA fragmentation analysis, we investigated the fragment size distribution of a gene family and calculated short fragment fraction (SFF). Methylation analyses evaluated the methylation levels of CG_16698623, a CG dinucleotide in the MGMT gene that we found hypermethylated in MTC tissues by analyzing public databases. The SFF ratio and methylation of CG_16698623 were significantly increased in plasma from MTC patients at diagnosis, and patients with clinical remission or stable disease at follow-up showed no significant SFF difference compared with healthy subjects. Our data support the diagnostic value of cfDNA traits that could enable better management of MTC patients.</abstract><cop>London</cop><pub>BioMed Central Ltd</pub><pmid>37726827</pmid><doi>10.1186/s40364-023-00522-4</doi><oa>free_for_read</oa></addata></record> |
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subjects | Analysis Biomarkers Calcitonin Cancer Carcinoma Cell-free DNA Circulating biomarker Circulating DNA fragmentation Circulating DNA methylation Correspondence Diagnosis DNA DNA fragmentation DNA methylation Epigenetics Genetic aspects Internet Medullary thyroid carcinoma Methylation Mutation Neuroendocrine tumors Rare tumour Remission Serum levels Size distribution Surgery Thyroid cancer Thyroid carcinoma Thyroid diseases Trends Tumors |
title | Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value |
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