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Concomitant RAS, RET/PTC, or BRAF Mutations in Advanced Stage of Papillary Thyroid Carcinoma.
- Source :
-
Thyroid . Aug2014, Vol. 24 Issue 8, p1256-1266. 11p. - Publication Year :
- 2014
-
Abstract
- Background: RET/PTC rearrangement, RAS, and BRAF mutations are considered to be mutually exclusive in papillary thyroid carcinoma (PTC). However, although concomitant mutations of RET/PTC, RAS, or BRAF have been reported recently, their significance for tumor progression and survival remains unclear. We sought to examine the prognostic value of concomitant mutations in PTC. Methods: We investigated 88 PTC for concomitant mutations. Mutation in BRAF exon 15, KRAS, NRAS, and HRAS were studied by polymerase chain reaction (PCR)-sequencing of tumor DNA; RET/PTC rearrangement was determined by reverse transcription (RT)-PCR-sequencing of tumor cDNA. Results: BRAF V600E was detected in 39 of 82 classic PTC (CPTC) and in all three tall-cell variants (49%, 42/85). KRAS mutation (p.Q61R and p.S65N) was detected in two CPTC (2%, 2/88) and NRASQ61R in one CPTC and two follicular variant PTC (FVPTC; 3%, 3/88). KRASS65N was identified for the first time in thyroid cancer and could activate mitogen-associated protein kinase (MAPK). RET/PTC-1 was detected in nine CPTC, one tall-cell variant, and two FVPTC. Concomitant BRAF V600E and KRAS, or BRAF V600E and RET/PTC-1 mutations were found in two CPTC, and six CPTC and one tall-cell variant, respectively. In total, 11 concomitant mutations were found in 88 PTC samples (13%), and most of them were in the advanced stage of disease (8/11, 73%; p<0.01). Conclusions: Our data show that concomitant mutations are a frequent event in advanced PTC and are associated with poor prognosis. The concomitant mutations may represent intratumor heterogeneity and could exert a gene dosage effect to promote disease progression. KRASS65N can constitutively activate the MAPK pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10507256
- Volume :
- 24
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Thyroid
- Publication Type :
- Academic Journal
- Accession number :
- 97162733
- Full Text :
- https://doi.org/10.1089/thy.2013.0610