A clinically applicable molecular classification of oncocytic cell thyroid nodules

Area of Science:

• Genomic instability in thyroid neoplasms
• Molecular diagnostics in oncology
• Cancer genomics

Background:

• Whole chromosome instability and genome haploidization are key drivers in oncocytic cell thyroid neoplasm (OCN) tumorigenesis.
• Copy number alterations (CNA) are less frequent in oncocytic thyroid adenoma (OA) than oncocytic carcinoma (OCA), suggesting a continuum.
• Understanding CNA patterns is crucial for differentiating benign from malignant OCN.

Purpose of the Study:

• To characterize copy number alteration (CNA) patterns in benign and malignant oncocytic cell thyroid neoplasms (OCN).
• To evaluate the utility of next-generation sequencing (NGS) based CNA-loss of heterozygosity (LOH) analysis for OCN diagnosis and risk stratification.
• To correlate CNA patterns with histopathological subtypes of OCN.

Main Methods:

• Utilized a next-generation sequencing (NGS) panel for genome-wide loss of heterozygosity (LOH) and chromosomal imbalance analysis across 30 OCN samples.
• Assessed 1500 single-nucleotide polymorphisms (SNPs) across all autosomes and the X chromosome.
• Validated CNA findings using DNA flow cytometry and whole-genome SNP array analysis.

Main Results:

• Genome haploidization (GH)-type CNA were found in 36% of OA and 88% of OCA.
• Endoreduplication was suspected in 50% of OCA, correlating with extensive GH-type CNA (P < 0.001).
• Reciprocal chromosomal imbalance CNA, associated with benign disease, were observed in 55% of OA.
• CNA patterns significantly differed between histopathological subgroups (P < 0.001).

Conclusions:

• NGS-based CNA-LOH analysis reveals distinct genomic patterns in benign versus malignant oncocytic thyroid neoplasms.
• These findings support the use of NGS for improved diagnosis and risk stratification of OCN.
• The study provides a framework for applying molecular diagnostics in routine OCN management.