Identification of differentially expressed genes in papillary thyroid carcinomas with and without rearrangements of the tyrosine kinase receptors RET and/or NTRK1.
BACKGROUND
The transforming capacities of RET and/or NTRK1 chimeric oncogenes as well as the molecular background of non-rearranged papillary thyroid carcinomas (PTCs) remain to be elucidated. To assess altered gene expression, we examined PTCs with and without tyrosine kinase receptor rearrangements by mRNA differential display (DD).


METHODS
Six of 13 PTCs examined harbored RET chimeras (3x RET/PTC1, 1x RET/PTC3) and/or NTRK1 chimeras (2x trk, 1x TRK-T3, 2 unknown TRK hybrids). The method of DD analysis was refined by a novel fragment-recovery technique using a high-performance fluorescence scanner.


RESULTS
Of 500 up- or down-regulated mRNA transcripts, 19 selected fragments were recovered, cloned, sequenced, and identified. The accuracy and high degree of reproducibility of the method was demonstrated. Differential expression of gene products with potential association to cell proliferation or tumor progression was observed, such as 14-3-3beta and Rab27a. Moreover, several gene products with unknown functions were demonstrated in PTCs bearing RET or NTRK1 hybrids versus rearrangement-negative PTCs, including a homologue of the Ig kappa light chain constant region.


CONCLUSIONS
Candidate transcripts with presumed tumorigenic potential in other solid tumors may prove to be relevant in the progression of PTCs, too. Most promising is the isolation of several differentially expressed, yet unknown, genes that may open new insights in the pathogenesis or progression of PTC.
Musholt
Thomas J
TJ
Endocrine Surgery, Johannes Gutenberg University Mainz, Mainz, Germany. thomas@musholt.com
Brehm
Christoph
C
Hanack
Julia
J
von Wasielewski
Reinhard
R
Musholt
Petra B
PB
D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics*; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D051096:Proto-Oncogene Proteins c-ret / Q000096:biosynthesis / Q000235:genetics*; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D015854:Up-Regulation
D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020917:Receptor, trkA