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

Oncogene. 2004 Sep 23;23(44):7436-40. doi: 10.1038/sj.onc.1207980.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Papillary / genetics
  • Amino Acid Substitution
  • Gene Expression Profiling / methods*
  • Gene Rearrangement
  • Genetic Variation
  • Humans
  • Italy
  • Mutation / genetics*
  • Mutation, Missense
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-raf / genetics*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, trkA / genetics*
  • Thyroid Neoplasms / genetics*


  • Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-raf