Role of BRAF and RAS Mutations in Extrathyroidal Extension in Papillary Thyroid Cancer

Cancer Genomics - Proteomics

JU HAN KIM²  JI YEON PARK²  CHAN HEE PARK²  KYU EUN LEE¹  YOUNGGYUN LIM²  JIN WOOK YI¹  KYE HWA LEE² 

[1] epartment of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Republic of Koreaancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Koreaepartment of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Republic of Koreaepartment of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Republic of Koreaancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Koreaancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Koreaepartment of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Republic of Koreaancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea;eoul National University Biomedical Informatics, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Koreaeoul National University Biomedical Informatics, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Koreaeoul National University Biomedical Informatics, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea

关键词: Papillary thyroid cancer;    extrathyroidal extension;    WNT signaling;    BRAF;    RAS;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

Background/Aim: Extrathyroidal extension (ETE) indicates the invasiveness of primary thyroid tumor into the adjacent tissue, and its importance as a prognostic factor overrides tumor size in classifying the cancer stage. The aim of this study was to determine the molecular basis of ETE in papillary thyroid carcinomas (PTCs). Materials and Methods: We systematically defined genes and pathways regulated in ETE using mutation and gene expression profiles from The Cancer Genome Atlas, and examined the effect of BRAF and RAS mutations on ETE. The significance of these genes was further validated using public microarray data. Results: Genes related to extracellular matrix and immune response were significantly up-regulated in ETE and ion-transport genes were often down-regulated. Differentiation properties and WNT signaling were also found to be altered by ETE. BRAF and RAS mutations were shown to have distinct effects on genes associated with ETE. Specifically, PAX8 and its downstream target WNT4 were differentially expressed according to mutation status in addition to ETE, indicating their critical roles in cell motility. Conclusion: BRAF V600E mutation predisposes PTC cells toward invasive phenotypes, while RAS mutation confers resistance to ETE. The differential regulation appears to be mediated through WNT4.

【 授权许可】

Unknown