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J Transl Med. 2018 Oct 1;16(1):269. doi: 10.1186/s12967-018-1642-0.

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

Author information

1
Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China.
2
Zhangjiang Center for Translational Medicine, Shanghai Biotecan Medical Diagnostics Co., Ltd, Shanghai, 201203, People's Republic of China.
3
Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yi-Shan Road, Shanghai, 200233, People's Republic of China. yangzhililaoshi@126.com.

Abstract

BACKGROUND:

Approximately half of the documented increases in differentiated thyroid carcinoma is due to identification of papillary thyroid microcarcinomas (PTMCs). Knowing whether PTMC is aggressive is required for proper treatment, but until now, there has been no method for assessing these traits and understanding the underlying mechanisms for aggressiveness.

METHODS:

We performed whole-exome sequencing of 16 PTMCs and matched normal thyroid tissues and GO/KEGG analysis to study genetic alterations and biological consequences associated with aggressive PTMCs, and then sequenced these genes using a next-generation gene-panel approach in an additional 70 PTMC samples including aggressive (n = 50) and non-aggressive (n = 20) groups.

RESULTS:

We identified 254 somatic mutations of 234 genes, for which 178 mutations in 168 genes were found in the aggressive group, and 76 mutations in 74 genes were found in the non-aggressive group. Several recurrent mutations in BRAF, VCAN, ALDH1L1, and MUC5B were identified, and many novel but infrequent mutations in other genes were also found. The aggressive cohort had more mutational burdens than the non-aggressive group (P = 0.004). Nonsynonymous mutations of 13 genes (MUC5B, TNN, SSPO, PPFIA1, PCDHGA2, ITGA8, ITGA4, DCHS1, CRNN, ROCK1, RELN, LAMC2, and AEBP1) were involved in cell adhesion, and these were only present in the aggressive group. Targeted sequencing of these genes revealed significant enrichment in the aggressive group (P = 0.000004).

CONCLUSION:

PTC may have evolved from PTMC due to sharing similar gene mutations, and the accumulation of such mutations promoted the aggressiveness of PTMC. Gene mutants associated with cell adhesion may be used to predict PTMC aggressiveness and allow more selective treatment.

KEYWORDS:

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

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