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A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are(More)
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(More)
Most human thyroid cancers are differentiated papillary carcinomas (PTC). Papillary thyroid microcarcinomas (PTMC) are tumors that measure 1 cm or less. This class of small tumors has proven to be a very common clinical entity in endocrine diseases. PTMC may be present in 30-40% of human autopsies and is often identified incidentally in a thyroid removed(More)
Papillary thyroid cancer (PTC) rates continue to increase in the United States and Europe, and, although most patients do well, some recur and die of their disease. Patients with PTC harboring the BRAF V600E mutation seem to display a more aggressive clinical behavior, but little is known about the role of this mutation in crucial processes in the tumor(More)
PURPOSE B-Raf(V600E) may play a role in the progression from papillary thyroid cancer to anaplastic thyroid cancer (ATC). We tested the effects of a highly selective B-Raf(V600E) inhibitor, PLX4720, on proliferation, migration, and invasion both in human thyroid cancer cell lines (8505c(B-RafV600E) and TPC-1(RET/PTC-1 and wild-type B-Raf)) and in primary(More)
Although B-Raf V600E is the most common somatic mutation in pap-illary thyroid carcinoma (PTC), how it induces tumor aggressiveness is not fully understood. Using gene set enrichment analysis and in vitro and in vivo functional studies, we identified and validated a B-Raf V600E gene set signature associated with tumor progression in PTCs. An independent(More)
PURPOSE FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene family that plays a role in certain tumor types. Here, we investigated the potential role of FOXA1 in human thyroid carcinomas. EXPERIMENTAL DESIGN We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in(More)
The incidence of human papillary thyroid cancer (PTC) is increasing and an aggressive subtype of this disease is resistant to treatment with vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor. VEGFR2 promotes angiogenesis by triggering endothelial cell proliferation and migration. However, the molecular mechanisms governing VEGFR2 stability in(More)
Even though several studies highlighted the role of maternal thyroid hormones (THs) during embryo-foetal development, direct evidence of their interaction with embryonic thyroid receptors (TRs) is still lacking. We generated a transgenic mouse model ubiquitously expressing a reporter gene tracing TH action during development. We engineered a construct(More)
BACKGROUND AND RATIONALE Anaplastic thyroid cancer (ATC) is characterized by pleomorphic cells, has a poor prognosis, is highly devastating disease, and is not curable. No reliable biomarkers of metastatic potential, helpful for early diagnosis of ATC and therapeutic response have been found yet. Thrombospondin-1 (TSP-1) plays a fundamental role in cancer(More)