Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid Cancer
The <i>BRAF</i> V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same pa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/30/3/227 |
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| author | Farzana Jasmine Briseis Aschebrook-Kilfoy Mohammad M. Rahman Garrett Zaagman Raymon H. Grogan Mohammed Kamal Habibul Ahsan Muhammad G. Kibriya |
| author_facet | Farzana Jasmine Briseis Aschebrook-Kilfoy Mohammad M. Rahman Garrett Zaagman Raymon H. Grogan Mohammed Kamal Habibul Ahsan Muhammad G. Kibriya |
| author_sort | Farzana Jasmine |
| collection | DOAJ |
| description | The <i>BRAF</i> V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same patients, on a genome-wide scale we tried to identify (a) any association between <i>BRAF</i> mutation and DNA promoter methylation, and (b) if the molecular findings may provide a basis for therapeutic intervention. We included 40 patients with TC (female = 28, male = 12) without distant metastasis. <i>BRAF</i> mutation was present in 18 cases. We identified groups of differentially methylated loci (DML) that are found in (a) both <i>BRAF</i> mutant and wild type, (b) only in <i>BRAF</i> mutant tumors, and (c) only in <i>BRAF</i> wild type. BRAF mutation-specific promoter loci were more frequently hypomethylated, whereas BRAF wild-type-specific loci were more frequently hypermethylated. Common DML were enriched in cancer-related pathways, including the mismatch repair pathway and Wnt-signaling pathway. Wild-type-specific DML were enriched in RAS signaling. Methylation status of checkpoint signaling genes, as well as the T-cell inflamed genes, indicated an opportunity for the potential use of <i>PDL1</i> inhibitors in BRAF mutant TC. Our study shows an association between <i>BRAF</i> mutation and methylation in TC that may have biological significance. |
| first_indexed | 2024-03-11T06:42:05Z |
| format | Article |
| id | doaj.art-a8f62edc747942d3ac147c4c825861a7 |
| institution | Directory Open Access Journal |
| issn | 1198-0052 1718-7729 |
| language | English |
| last_indexed | 2024-03-11T06:42:05Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj.art-a8f62edc747942d3ac147c4c825861a72023-11-17T10:31:01ZengMDPI AGCurrent Oncology1198-00521718-77292023-03-013032978299610.3390/curroncol30030227Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid CancerFarzana Jasmine0Briseis Aschebrook-Kilfoy1Mohammad M. Rahman2Garrett Zaagman3Raymon H. Grogan4Mohammed Kamal5Habibul Ahsan6Muhammad G. Kibriya7Institute for Population and Precision Health, Biological Sciences, University of Chicago, Chicago, IL 60637, USAInstitute for Population and Precision Health, Biological Sciences, University of Chicago, Chicago, IL 60637, USADepartment of Pathology, Bangabandhu Sheikh Mujib Medical University, Dhaka 1000, BangladeshInstitute for Population and Precision Health, Biological Sciences, University of Chicago, Chicago, IL 60637, USADepartment of Surgery, Baylor St. Luke’s Medical Center, Houston, TX 77030, USADepartment of Pathology, The Laboratory, Dhaka 1205, BangladeshInstitute for Population and Precision Health, Biological Sciences, University of Chicago, Chicago, IL 60637, USAInstitute for Population and Precision Health, Biological Sciences, University of Chicago, Chicago, IL 60637, USAThe <i>BRAF</i> V600E mutation and DNA promoter methylation play important roles in the pathogenesis of thyroid cancer (TC). However, the association of these genetic and epigenetic alterations is not clear. In this study, using paired tumor and surrounding normal tissue from the same patients, on a genome-wide scale we tried to identify (a) any association between <i>BRAF</i> mutation and DNA promoter methylation, and (b) if the molecular findings may provide a basis for therapeutic intervention. We included 40 patients with TC (female = 28, male = 12) without distant metastasis. <i>BRAF</i> mutation was present in 18 cases. We identified groups of differentially methylated loci (DML) that are found in (a) both <i>BRAF</i> mutant and wild type, (b) only in <i>BRAF</i> mutant tumors, and (c) only in <i>BRAF</i> wild type. BRAF mutation-specific promoter loci were more frequently hypomethylated, whereas BRAF wild-type-specific loci were more frequently hypermethylated. Common DML were enriched in cancer-related pathways, including the mismatch repair pathway and Wnt-signaling pathway. Wild-type-specific DML were enriched in RAS signaling. Methylation status of checkpoint signaling genes, as well as the T-cell inflamed genes, indicated an opportunity for the potential use of <i>PDL1</i> inhibitors in BRAF mutant TC. Our study shows an association between <i>BRAF</i> mutation and methylation in TC that may have biological significance.https://www.mdpi.com/1718-7729/30/3/227thyroid carcinoma<i>BRAF</i> mutationmethylationRAS signalingTNFR2 |
| spellingShingle | Farzana Jasmine Briseis Aschebrook-Kilfoy Mohammad M. Rahman Garrett Zaagman Raymon H. Grogan Mohammed Kamal Habibul Ahsan Muhammad G. Kibriya Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid Cancer Current Oncology thyroid carcinoma <i>BRAF</i> mutation methylation RAS signaling TNFR2 |
| title | Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid Cancer |
| title_full | Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid Cancer |
| title_fullStr | Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid Cancer |
| title_full_unstemmed | Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid Cancer |
| title_short | Association of DNA Promoter Methylation and <i>BRAF</i> Mutation in Thyroid Cancer |
| title_sort | association of dna promoter methylation and i braf i mutation in thyroid cancer |
| topic | thyroid carcinoma <i>BRAF</i> mutation methylation RAS signaling TNFR2 |
| url | https://www.mdpi.com/1718-7729/30/3/227 |
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