No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan.
OBJECTIVE
Genetic alterations in four oncogenes, namely RAS point mutations, RET rearrangements (RET/PTC), NTRK1 rearrangements (TRK) and BRAF point mutations have been identified in human papillary thyroid carcinomas (PTCs). These oncogenes act along the RET/PTC(TRK)-RAS-BRAF-MEK-MAPK kinase pathway, mediating a number of cellular fates including growth, proliferation and survival in thyroid cells. In this study, we analysed mutations of BRAF in a cohort of PTCs.


METHODS
To screen for BRAF mutations, the genomic DNA of 105 PTCs were amplified by polymerase chain reaction (PCR) with primers flanking exon 15 and PCR products were directly sequenced with an automatic sequencer. These results, together with data from our previous studies on RAS, RET rearrangements and NTRK1 rearrangements in the same tumours, were compared to determine their individual significance in the pathogenesis of PTCs in Taiwan.


RESULTS
BRAF mutations were detected in 49 of 105 (47%) tumour samples. All mutations involved a thymine-to-adenine transversion at nucleotide 1799 and were heterozygous. There was no overlap between papillary carcinomas harbouring RET rearrangements, NTRK1 rearrangements and BRAF mutations. In this cohort, correlation between BRAF mutations and various clinicopathological parameters in 101 papillary carcinomas did not reveal any association with age at diagnosis, sex, tumour size, histological variants of PTC, multicentricity, cervical lymph node metastases, extrathyroidal invasion, distant metastases and clinical stage.


CONCLUSIONS
BRAFV600E mutation is the most prevalent oncogene in PTCs in Taiwan. Our data did not suggest that BRAFV600E mutation could be a potentially useful marker of prognosis in patients with papillary carcinomas in the population studied.
Liu
Rue-Tsuan
RT
Division of Metabolism, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC.
Chen
Yi-Ju
YJ
Chou
Fong-Fu
FF
Li
Chun-Liang
CL
Wu
Wei-Li
WL
Tsai
Po-Chin
PC
Huang
Chao-Cheng
CC
Cheng
Jiin-Tsuey
JT
D000328:Adult; D000367:Age Factors; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017354:Point Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018709:Statistics, Nonparametric; D013624:Taiwan; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf