Genomic profiling of lymph node and distant metastases from papillary and poorly differentiated thyroid carcinomas

Valdemar Máximo ^1,2,3, Miguel Melo ^1,2,3,4, Manuel Sobrinho-Simões ^1,2,3,5

⁰i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.

Endocrine +

|

July 19, 2024

View abstract on PubMed

Summary

Metastases from papillary thyroid cancer (PTC) and poorly differentiated thyroid cancer (PDTC) show distinct molecular alterations based on location. These include mutations in NRAS, RBM10, and SDHA amplifications, offering potential therapeutic targets.

Area Of Science

Oncology
Molecular Biology
Genomics

Background

Papillary thyroid carcinoma (PTC) and poorly differentiated thyroid carcinoma (PDTC) are significant thyroid malignancies.
Understanding the molecular landscape of their metastases is crucial for targeted therapy development.

Purpose Of The Study

To conduct a comprehensive molecular profiling of metastases originating from PTC and PDTC.
To identify location-specific genomic alterations in thyroid cancer metastases.

Main Methods

Analysis of targeted DNA sequencing data from 136 PTC and 35 PDTC metastases obtained from cBioPortal.
Evaluation of clinicopathological features including metastasis number and location.
Assessment of genomic alterations such as mutations, translocations, copy number alterations, and fraction of genome altered (FGA).

Main Results

Bone metastases from PTC showed lower BRAF mutation frequency (43%) but higher RBM10 and NRAS mutations (21%) compared to lymph node metastases (LNMs) (88% BRAF, 3% NRAS/RBM10).
Lung metastases from PTC exhibited increased RET translocations (15%) compared to LNMs (3%).
SDHA gene amplifications were found in 38% of PDTC bone metastases but were absent in LNMs.

Conclusions

Thyroid cancer metastases harbor distinct, clinically relevant molecular alterations based on anatomical site.
Identified alterations, including NRAS/RBM10 mutations, RET translocations, and SDHA amplifications, represent potential therapeutic targets for metastatic PTC and PDTC.

Keywords:

Copy number alterations DNA sequencing Distant metastasis Papillary thyroid carcinomas Poorly differentiated thyroid carcinomas Somatic mutations