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Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer

Oncogene volume 23, pages 7436–7440 (2004)Cite this article

Abstract

Papillary thyroid carcinoma (PTC) is associated with RET and NTRK1 rearrangements and BRAF mutations. A series of 60 PTCs collected in a single center from Italian patients were histologically re-examined and subclassified as well differentiated or tall cell variant. The sample collection was analysed for the presence of all the reported PTC-associated genetic alterations through DNA or cDNA amplification, followed by automated sequencing. The analysis of exons 11 and 15 of BRAF gene revealed the T1796A (V599E) mutation in 32% of cases, and this alteration is significantly associated with PTC tall cell variant. Oncogenic rearrangements of RET and NTRK1 receptors were found in 33 and 5% of cases, respectively. No Ras mutations were detected. Overall, genetic alterations were detected in two-thirds of samples, and in no single case more than one mutational event was found simultaneously. Gene expression profiling of a subset of 31 tumors performed using cDNA microarray chips showed no strong differences in global gene expression among the different cases. However, a supervised analysis of the obtained data identified a subset of genes differentially expressed in tumors carrying BRAF mutation or RTK rearrangement.

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Acknowledgements

We thank Donata Penso and Sara Perugini for performing nucleotide sequencing, James Reid and Lara Lusa for statistical analysis and Cristina Mazzadi for secretarial assistance. This work was supported by AIRC Grant, CNR-MIUR ‘Progetto Strategico Oncologia’ (02.00385.ST97 to MA Pierotti).

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Authors and Affiliations

  1. Department of Pathology, Experimental Molecular Pathology, Istituto Nazionale Tumori, Milan, Italy

    Milo Frattini, Debora Balestra, Paola Collini & Silvana Pilotti

  2. Department of Experimental Oncology, Operative Unit ‘Molecular Mechanisms of Cancer Growth and Progression’, Istituto Nazionale Tumori, Via G Venezian, 1, Milan, 20133, Italy

    Cristina Ferrario, Paola Bressan, Loris De Cecco, Piera Mondellini, Italia Bongarzone, Manuela Gariboldi, Marco A Pierotti & Angela Greco

  3. IFOM Foundation (The Firc Institute for Molecular Oncology Foundation), Milan, Italy

    Cristina Ferrario, Loris De Cecco, Manuela Gariboldi & Marco A Pierotti

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  1. Milo Frattini
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  2. Cristina Ferrario
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  11. Marco A Pierotti
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Correspondence to Marco A Pierotti or Angela Greco.

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Frattini, M., Ferrario, C., Bressan, P. et al. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene 23, 7436–7440 (2004). https://doi.org/10.1038/sj.onc.1207980

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