Comparative genomic hybridization, BRAF, RAS, RET, and oligo-array analysis in aneuploid papillary thyroid carcinomas

• DOI: 10.3892/or.18.4.917
• Publication Date: 2014-03-10T07:50:49Z
• Authors: Raquel Rodrigues; Lúcia Roque; Carla Espadinha; António Pinto; Rita Domingues; Joana Dinis; Ana Catarino; Teresa Pereira; Valeriano Leite
• Keywords: Adult; Aged, 80 and over; Gene Rearrangement; Male; Proto-Oncogene Proteins B-raf; Gene Expression Profiling; Nucleic Acid Hybridization; Middle Aged; Aneuploidy; Flow Cytometry; Carcinoma, Papillary; 3. Good health; Immunoenzyme Techniques; 03 medical and health sciences; Genes, ras; 0302 clinical medicine; Adenocarcinoma, Follicular; Biomarkers, Tumor; Humans; Female; Discoidin Domain Receptors; Aged; Oligonucleotide Array Sequence Analysis

Aneuploidy in papillary thyroid carcinomas (PTCs) is considered a marker of worse prognosis. Multiple genetic surveys have been performed in PTCs, however, we are not aware of any such studies in aneuploid PTCs. In order to contribute to a better comprehension of the genetic basis of this neoplasm's more aggressive behaviour in 17 aneuploid PTCs we performed a comparative genomic hybridization (CGH) analysis, studied the BRAF and RAS mutational status, searched for RET/PTC1 and RET/PTC3 rearrangements and determined their expression profile. Array results were validated by TaqMan and immunohistochemistry. CGH revealed multiple non-random chromosomal abnormalities. BRAFV600E and RAS mutations were found in 41.2% and 33% of the carcinomas respectively. None of the studied cases presented RET/PTC1 or RET/PTC3 rearrangement. When comparing array data with the chromosomal, mutational and clinical data we found that: a) loss of control of cellular transcription was of major relevance in this group of neoplasms, HMGA2 being one of the most overexpressed genes; b) gene expression correlated with the mutational status of PTCs, as in BRAF+ cases cMET and FN1 were concomitantly overexpressed; and c) death from disease and distant metastasis was associated to the overexpression of DDR2 and to the down-regulation of genes involved in immune, inflammatory response, signal transduction and cell adhesion processes. In conclusion we have identified in aneuploid PTCs a group of significantly altered molecules that may represent preferential targets for the development of new more efficient therapies in this type of cancer.