Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer.
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.
Department of Pathology, Experimental Molecular Pathology, Istituto Nazionale Tumori, Milan, Italy.
Milo
M
Frattini
Cristina
C
Ferrario
Paola
P
Bressan
Debora
D
Balestra
Loris
L
De Cecco
Piera
P
Mondellini
Italia
I
Bongarzone
Paola
P
Collini
Manuela
M
Gariboldi
Silvana
S
Pilotti
Marco A
MA
Pierotti
Angela
A
Greco
D000231:Adenocarcinoma, Papillary / Q000235:genetics; D019943:Amino Acid Substitution; D020869:Gene Expression Profiling / Q000379:methods*; D015321:Gene Rearrangement; D014644:Genetic Variation; D006801:Humans; D007558:Italy; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020917:Receptor, trkA / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
D015513:Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf