ETA2024 Poster Presentations Translational thyroid cancer research-2 (10 abstracts)
DNA methylation in the thyroid tumors with known gene alteration
Karolina Mastnikova 1 , Barbora Bulanova 2 , Vlasta Kuklikova 2 , Eliska Vaclavikova 2 , Jitka Carkova 2 , Rami Katra 3 , Petr Vlcek 4 , Daniela Kodetova 5 , Martin Chovanec 6 , Jana Drozenova 7 , Radoslav Matej 7 , Jaromir Astl 8 , Jiri Hlozek 8 , Jiri Soukup 9 , Josef Vcelak 2 & Bela Bendlova 2
1Institute of Endocrinology, Department of Molecular Endocrinology, Prague, Czech Republic; 2Institute of Endocrinology, Department of Molecular Endocrinology, Czech Republic; 32nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Ear, Nose, and Throat, Czech Republic; 42nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Nuclear Medicine and Endocrinology, Czech Republic; 52nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Department of Pathology and Molecular Medicine, Czech Republic; 63rd Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Department of Otorhinolaryngology, Czech Republic; 73rd Faculty of Medicine, Charles University in Prague and University Hospital Kralovske Vinohrady, Department of Pathology, Czech Republic; 83rd Faculty of Medicine and Military University Hospital, Department of Otorhinolaryngology and Maxillofacial Surgery, Czech Republic; 93rd Faculty of Medicine and Military University Hospital, Department of Pathology, Czech Republic
Objectives: Molecular testing of thyroid tumors is increasingly being used for the diagnosis and prognosis of patients. In some cases, however, the same gene variant may be present in both benign and malignant thyroid tissue. The issue is also a different nature (aggressiveness) of carcinomas of the same genetic origin. Comparing of DNA methylation profiles of these samples could be a possible way of distinguishing these cases. Aim of this pilot study was to analyze the DNA methylation profiles of samples with a known gene variant and to find possible differences between the cohorts.
Methods: The study consisted of 48 fresh frozen thyroid tissues samples with a known molecular profile: 16 papillary thyroid carcinomas (PTCs) harboring BRAF V600E, 12 PTCs with RET/PTC1 rearrangement, 12 NRAS Q61R (four benign nodules, four low risk neoplasms, four PTCs), and eight healthy thyroid tissues (with no genetic alteration). Extracted DNA was used for next-generation sequencing using the TruSeqTM Methyl Capture EPIC Library Prep Kit (Illumina). Bioinformatics to compare cohorts of NRAS benign vs. malignant, BRAF indolent vs. aggressive PTCs and RET/PTC1 indolent vs. aggressive PTCs was performed by BaseSpace MethylKit App (Illumina).
Results: Differential methylation profile was obtained by comparing the cohorts. NRAS carcinomas differed from benign NRAS nodules in CpG islands with possible influence on RGPD8, RMRP and ANKRD7 genes, where hypermethylated CpGs were most abundant in carcinomas. Most hypomethylated CpGs were in CpG islands with possible influence on the IHO1, ATP9B, HLA-DQB2 genes. Aggressive BRAF carcinomas differentiated from indolent BRAF thyroid carcinomas in hypermethylation of CpGs around the SCO2, TYMP, ODF3B, DMRTA2, TRIL genes. On the other hand, representations of a higher number of hypomethylated CpGs in the islands was not so frequent. RET/PTC1 gene rearrangements of aggressive nature had most hypermethylated CpGs in CpG islands with occurrence of SP9, HCN1, TMEM229A, GSG1L genes. There were less hypomethylation sites in this cohort too.
Conclusion: In summary, differential methylation of thyroid tumors with the same genetic alteration could be a useful tool for better diagnostics and prognostics. Analysis of a lager sample set will follow.
Supported by AZV NU21-01-00448 and MH CZ RVO 00023761.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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