Three-dimensional telomere profiles in papillary thyroid cancer variants: A pilot study

Area of Science:

• Oncology
• Genetics
• Cell Biology

Background:

• Papillary thyroid carcinoma (PTC) has several variants, including classical PTC (CL-PTC) and follicular variant PTC (FV-PTC).
• Encapsulated FV-PTC was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to benign lesion similarities.
• Specific molecular signatures for NIFTP are lacking, and telomere dysfunction is linked to genomic instability in cancer.

Purpose of the Study:

• To investigate if a unique 3D nuclear telomere architecture characterizes NIFTP.
• To determine if 3D telomere structure can differentiate NIFTP from other PTC histologic variants.
• To explore the relationship between telomere length and NIFTP classification.

Main Methods:

• Pilot study evaluating 3D nuclear telomere architecture.
• Comparative analysis of telomere profiles across NIFTP, CL-PTC, FV-PTC, and follicular thyroid adenoma (FTA).
• Assessment of BRAF expression and its association with telomere length.

Main Results:

• Significant differences found in 3D telomere profiles between NIFTP and CL-PTC/FV-PTC.
• NIFTP demonstrated longer telomeres, overlapping with those of FTA.
• No correlation observed between BRAF expression and telomere length in any tested sample.

Conclusions:

• NIFTP possesses distinct 3D telomere architecture compared to malignant PTC variants.
• NIFTP's telomere characteristics align more closely with benign follicular thyroid adenoma.
• Findings support NIFTP's classification closer to non-malignant thyroid nodules and highlight shorter telomeres in PTC.