Identification of insertions in PTEN and TP53 in anaplastic thyroid carcinoma with angiogenic brain metastasis.

Patients with undifferentiated (anaplastic) thyroid carcinoma (ATC) are refractory to surgical treatment, chemotherapy, and/or radiotherapy, and have a dismal prognosis (Smallridge et al. 2012). Distant metastasis occurs at various sites and is poorly sensitive to chemotherapy or radiotherapy. As a result of aggressive tumor behavior and ineffective therapeutic efficacy, patients do poorly (Besic & Gazic 2013). Positron emission tomography (PET)/computed tomography (CT) is the primary imaging modality for ATC at initial staging and has utility in the early evaluation of treatment response and follow-up (Poisson et al. 2010). Distant metastases, extensive local infiltration, and regional lymph node metastases have been found at autopsy in 91, 76, and 51% of cases respectively. Regional and distant metastases are shown to be present in 51% of cases, with 40% of cases showing distant metastases alone. The most common site of metastasis is the lung (78%), followed by intrathoracic lymph nodes (58%), neck lymph nodes (51%), pleura (29%), adrenal glands (24%), liver (20%), brain (18%), and heart (18%) (Besic & Gazic 2013). Lung metastases are present in 34 of 38 (89%) cases, with distant metastases found at autopsy, and are known to be present in 27 of these patients while alive. In most patients, lung metastases are detected by chest X-ray (Besic & Gazic 2013). Several genetic alterations are reported in the pathogenesis of ATC, including RAS, BRAF, TP53, CTNNB1 (b-catenin), VEGFR1, VEGFR2, KIT, MET, PIK3C, FOXA1, etc. (Liu et al. 2008, Nucera et al. 2009, Smallridge et al. 2012, Antonello & Nucera 2013). The BRAF mutation is the most prevalent genetic alteration in PTC (frequency of about 60%) and may be associated with tumor progression of PTC to ATC (frequency: about 15–44%) (Ricarte-Filho et al. 2009, Cancer Genome Atlas Research Network 2014, Shi et al. 2015). Importantly, although pre-clinical (Nehs et al. 2010, 2012) and clinical