title: The BRAFV600E mutation: what is it really orchestrating in thyroid cancer?
abstract: BRAFV600E is a constitutively active onco-kinase and is the most common genetic alteration in papillary thyroid carcinoma (PTC), and in anaplastic thyroid carcinoma as well, albeit at a lower frequency. The BRAFV600E mutation in some studies has been significantly associated with extra-thyroidal extension, metastases, recurrence, and mortality in patients with PTC. A recent genome-wide expression profiling approach (Gene Set Enrichment Analysis (GSEA)) and in vitro and in vivo functional studies revealed that BRAFV600E affects extracellular matrix composition (i.e. increased expression of some collagens and laminins) and promotes thyroid cancer migration and invasion. BRAFV600E through the phospho-MEK1/2 and phospho-ERK1/2 pathway may control a network of genes crucial in integrating and regulating the extracellular and intracellular signaling in thyroid cancer cells, which may be fundamental to trigger an abnormal cell differentiation/totipotency and shape/polarity, and contribute to tumor aggressiveness mechanisms (i.e. cell adhesion, migration, and invasion). Increasing our knowledge of BRAFV600E-modulated ECM genes and targeting the subset of genes essential for tumor aggressiveness will help establish a novel paradigm for treatment of thyroid cancers harboring BRAFV600E. Furthermore, identifying downstream events from the BRAFV600E/ERK1/2 pathway will eventually identify novel biomarkers that can be used to correlate with disease outcome and overall survival.
authors.affiliation: Thyroid Cancer Research Laboratory, Endocrine Surgery Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.|Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Nucera
authors.affiliation: Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Lawler
authors.affiliation: Thyroid Cancer Research Laboratory, Endocrine Surgery Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Hodin
authors.affiliation: Thyroid Cancer Research Laboratory, Endocrine Surgery Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Sareh
authors.initials: S
authors.lastname: Parangi
mesh_terms: D019943:Amino Acid Substitution / Q000502:physiology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002277:Carcinoma; D002291:Carcinoma, Papillary; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D020125:Mutation, Missense / Q000502:physiology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000502:physiology; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014633:Valine / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine