Molecular Pathology of Anaplastic Thyroid Carcinomas: A Retrospective Study of 144 Cases

• DOI: 10.1089/thy.2016.0254
• Publication Date: 2017-03-29T06:27:43Z
• Authors: Benjamin Bonhomme; Yann Godbert; Gaelle Perot; Abir Al Ghuzlan; Stéphane Bardet; Geneviève Belleannée; Lise Crinière; Christine Do Cao; Geneviève Fouilloux; Serge Guyetant; Antony Kelly; Sophie Leboulleux; Camille Buffet; Emmanuelle Leteurtre; Jean-Jacques Michels; Frédérique Tissier; Marie-Elisabeth T...; Michel Wassef; Clémence Pinard; Isabelle Hostein; Isabelle Soubeyran
• Keywords: Molecular Pathology

Background: Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were determine the frequency anaplastic lymphoma kinase (ALK) translocations identify mutational profile ATC including TERT promoter mutations. Methods Materials: One hundred forty-four cases collected from 10 centers that are part national French network for management refractory tumors. Fluorescence in situ hybridization analysis ALK rearrangement was performed on tissue microarrays. A panel 50 genes using next-generation sequencing mutations Sanger also screened. Results: interpretable 90 (62.5%) cases. (1.1%) case positive an borderline threshold (15% cells). Next-generation results 94 (65.3%) cases, (TERT) 98 (68.1%) total 210 (intronic exonic) identified. TP53 alterations most frequent (54.4%). Forty-three percent harbored mutation (H-K-N)RAS genes, 13.8% BRAF gene (essentially p.V600E), 17% PI3K-AKT pathway mutation, 6.4% both RAS PI3K mutations, 4.3% PTEN Nearly 10% showed no RAS, pathways, or TP53, ALK, ATM, APC, CDKN2A, ERBB2, RET, SMAD4, not yet described Genes encoding potentially druggable targets included: ATM four (4.3%) ERBB2 one case, MET case. alteration found 53 (54.0%) 43 C228T C250T Three out our did harbor interest. Conclusion: This confirms rearrangements landscape heterogeneous, many implicated follicular epithelial cell dedifferentiation process. may explain effectiveness targeted tested so far.