Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

中文翻译：

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乳头状甲状腺癌变体中的三维端粒图谱：一项初步研究。

除了乳头状甲状腺癌 (PTC) 的两种主要组织学类型，经典 PTC (CL-PTC) 和滤泡型 PTC (FV-PTC)，还描述了其他几种变体。由于与良性病变相似，封装的 FV-PTC 变体最近被重新分类为具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤 (NIFTP)。然而，具体的分子特征仍然不可用。众所周知，对功能失调的端粒进行不当的 DNA 修复可能会导致端粒相关的基因组不稳定。受损端粒修复过程中涉及的机制可能导致有害结果，改变癌细胞中的三维 (3D) 核端粒和基因组组织。这项试点研究旨在评估特定的 3D 核端粒结构是否可以表征 NIFTP，可能将其与其他 PTC 组织学变体区分开来。我们的研究结果表明，CL-PTC 和 FV-PTC 的 3D 端粒谱与 NIFTP 不同，并且 NIFTP 更类似于滤泡性甲状腺腺瘤 (FTA)。NIFTP 的端粒比 CL-PTC 和 FV-PTC 样本更长，并且 NIFTP 的端粒长度与 FTA 组织型的端粒长度重叠。相反，在所有测试样本中，BRAF 表达与端粒长度之间没有关联。这些初步发现强化了 NIFTP 更接近非恶性甲状腺结节的观点，并证实 PTC 具有短端粒。NIFTP 的端粒比 CL-PTC 和 FV-PTC 样本更长，并且 NIFTP 的端粒长度与 FTA 组织型的端粒长度重叠。相反，在所有测试样本中，BRAF 表达与端粒长度之间没有关联。这些初步发现强化了 NIFTP 更接近非恶性甲状腺结节的观点，并证实 PTC 具有短端粒。NIFTP 的端粒比 CL-PTC 和 FV-PTC 样本更长，并且 NIFTP 的端粒长度与 FTA 组织型的端粒长度重叠。相反，在所有测试样本中，BRAF 表达与端粒长度之间没有关联。这些初步发现强化了 NIFTP 更接近非恶性甲状腺结节的观点，并证实 PTC 具有短端粒。