Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer

• Published in: International journal of molecular sciences 2018-09, Vol.19 (10), p.2867
• Main Authors: Lee, Woo Kyung, Lee, Seul Gi, Yim, Seung Hyuk, Kim, Daham, Kim, Hyunji, Jeong, Seonhyang, Jung, Sang Geun, Jo, Young Suk, Lee, Jandee
• Format: Article
• Language: English
• Subjects: Carcinoma, Papillary - genetics; Carcinoma, Papillary - secondary; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Movement; Cell Proliferation; Exome; hedgehog proteins; High-Throughput Nucleotide Sequencing; Humans; Lymphatic Metastasis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mutation, Missense; neoplasm invasiveness; thyroid cancer; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Tumor Cells, Cultured; Whole Exome Sequencing
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms19102867

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide 'A' at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.