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Cell adhesion-related gene somatic mutations are enriched in aggressive papillary thyroid microcarcinomas

Jianlu Song¹, Shouxin Wu², Xiaotian Xia¹

¹Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.

Journal of Translational Medicine

|October 5, 2018

Summary

Papillary thyroid microcarcinomas (PTMCs) aggressiveness can now be predicted using gene mutations. Cell adhesion gene mutations are key indicators for identifying aggressive PTMC, enabling more targeted treatments.

Area of Science:

Oncology
Genetics
Molecular Biology

Background:

Papillary thyroid microcarcinomas (PTMCs) account for half of differentiated thyroid carcinoma diagnoses.
Assessing PTMC aggressiveness is crucial for effective treatment, but methods have been lacking.
Understanding the genetic mechanisms underlying PTMC aggressiveness is essential.

Purpose of the Study:

To identify genetic alterations associated with aggressive PTMCs.
To understand the biological consequences of these genetic changes.
To develop a method for predicting PTMC aggressiveness.

Main Methods:

Whole-exome sequencing of 16 PTMCs and matched normal tissues.
Gene Ontology (GO) and KEGG pathway analysis.
Next-generation gene-panel sequencing of 70 PTMC samples (50 aggressive, 20 non-aggressive).

Main Results:

Identified 254 somatic mutations in 234 genes; 178 mutations in 168 genes were in the aggressive group.
Found recurrent mutations in BRAF, VCAN, ALDH1L1, and MUC5B.
Discovered 13 cell adhesion-related genes with mutations exclusively in the aggressive PTMC group, significantly enriched (P=0.000004).

Conclusions:

PTMC aggressiveness is promoted by the accumulation of gene mutations, potentially leading to papillary thyroid carcinoma (PTC) evolution.
Mutations in cell adhesion genes can predict PTMC aggressiveness.
These findings enable more selective treatment strategies for PTMC.

Keywords:

Aggressiveness Cell adhesion Papillary thyroid microcarcinoma Somatic mutation Whole-exome sequencing

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