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Review
. 2021 May 1;10(5):1082.
doi: 10.3390/cells10051082.

The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy

Amandeep Singh  1   2   3 , Jeehoon Ham  1   3   4 , Joseph William Po  4   5 , Navin Niles  1   4   6 , Tara Roberts  7 , Cheok Soon Lee  1   2   3   4   8   9   10
Affiliations
Review

The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy

Amandeep Singh et al. Cells. .

Abstract

Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.

Keywords: PD-L1; genomics; immunotherapy; microenvironment; thyroid cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genetic alterations involved in the evolution of thyroid cancers. Figure adapted from Pozdeyez et al. [18]. Rat sarcoma (RAS). V-raf murine sarcoma viral oncogene homolog B1(BRAF). Rearranged during transfection (RET). Anaplastic lymphoma kinase (ALK). Paired box gene 8-peroxisome proliferator-activated receptor (PAX8-PPARγ). Telomerase reverse transcriptase (TERT). Tumour protein 53 (TP53). Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B). (PIK3CA). Phosphatase and tensin homolog (PTEN). Ak strain transforming (AKT). Guanine nucleotide binding protein, alpha stimulating activity polypeptide (GNAS). Retinoblastoma1 (RB1). AT-rich interactive domain-containing protein 2 (ARID2). Neurofibromatosis1 (NF1). V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT). Mismatch repair (MMR). Papillary thyroid carcinoma (PTC). Follicular thyroid carcinoma (FTC). Medullary thyroid carcinoma (MTC). Anaplastic thyroid carcinoma (ATC).
Figure 2
Figure 2
Commonly dysregulated cell signalling mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase (P13K)/Ak strain transforming (AKT) and wingless-related integration site (WNT) pathways in thyroid cancers.
See this image and copyright information in PMC

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