ECE2020 Audio ePoster Presentations Thyroid (144 abstracts)
Loss of heterozygosity (LOH) at 12q24.11 as a potential marker of follicular thyroid lesions malignancy
Martyna Borowczyk 1 , Ewelina Szczepanek-Parulska 1 , Bartłomiej Budny 1 , Szymon Dębicki 1 , Frederik Verburg 2 , Dorota Filipowicz 1 , Elżbieta Wrotkowska 1 , Lidia Gil 3 , Małgorzata Janicka-Jedyńska 4 , Michalina Oszywa 1 , Katarzyna Ziemnicka 1 & Marek Ruchala 1
1Poznan University of Medical Sciences, Department of Endocrinology, Metabolism and Internal Medicine, Poznan, Poland; 2University Hospital Marburg, Department of Nuclear Medicine, Marburg, Germany; 3Poznan University of Medical Sciences, Department of Hematology and Bone Marrow Transplantation, Poznan, Poland; 4Poznan University of Medical Sciences, Department of Clinical Pathology, Poznań, Poland
Introduction: Pre- and postsurgical differentiation between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC) represents a significant diagnostic challenge. Typical markers of malignancy may appear as specific genetic alterations. Next-generation sequencing (NGS) studies bring information about single point mutations, however better insight into follicular thyroid lesions genetic landscape, encompassing bigger rearrangements, is needed.
Aim: The study aimed to compare FTA and FTC using the high-resolution single nucleotide polymorphism (SNP) array and identify recurrent regions of LOH (loss of heterozygosity), which may support preoperative differentiation and a better understanding of those entities.
Material and Methods: We analyzed formalin-fixed paraffin-embedded (FFPE) samples acquired from 32 patients, Caucasians (median age at diagnosis: 58), diagnosed with follicular thyroid lesions: 16 diagnosed with FTA and 16 diagnosed with FTC. Both groups were adjusted for age and gender. Genomic DNA was isolated from dissected FFPE tissues using QIAamp DNA FFPE Tissue Kit (Roche). The OncoScan array (Affymetrix, Thermo Fisher) was used to determine structural rearrangements and LOH utilizing the SNP markers. The obtained data from genomic experiments was subjected for analysis using dedicated OncoScan Console 1.3 and ChAS v4 software and compared with clinical data.
Results: The most common LOH present in both FTA (63%) and FTC (69%) was 16p12.1p11.1 LOH (7.50 Mb in size) that encompasses TP53G3 and its several alternative splicing transcripts (TP53G3B, TP53G3C, TP53G3D). The only LOH present exclusively in FTA patients (56% vs 0%) was 11p11.2p11.12 (5.40 Mb), including KAI1, a metastasis suppressor gene. Another LOH on chromosome 20 (q11.21-q11.23, 6.89 Mb) predominated also in FTA (31% vs 6%, P = 0.172). The alteration which tended to be detected more often in FTC (38% vs 6%, P = 0.083) was 12q24.11q24.13 (3.99 Mb) overlapping FOXN4, MYL2, PTPN11, RASAL1genes (with a suspected role in tumor progression). Another two LOH occurred with a similar frequency in both FTC and FTA (56% vs 44%, and 56% vs 31%): 3p21.31p21.1 (6.40 Mb) encompassing SMARCC1, FBXW12, PARP3 and 15q15.1q21.1 (3.62 Mb) including TYRO3.
Conclusions: The results indicate that FTA and FTC may share a common genetic background, even though differentiating rearrangements may also be detected. 12q24.11q24.13 LOH may constitute a possible marker of malignancy as it includes genes directly associated with thyroid cancer pathogenesis. Genomic screening demonstrates the complexity of follicular thyroid lesions’ genetic background and enables the identification of new genetic rearrangements contributing to FTC pathogenesis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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