Korean J Intern Med.  2010 Dec;25(4):399-407. 10.3904/kjim.2010.25.4.399.

Microarray Analysis of Papillary Thyroid Cancers in Korean

• Kim HS
• Kim DH
• Kim JY
• Jeoung NH
• Lee IK
• Bong JG
• Jung ED

• KMID: 964721
• DOI: http://doi.org/10.3904/kjim.2010.25.4.399

Abstract

BACKGROUND/AIMS
Papillary thyroid cancer (PTC) is the most common malignancy of the thyroid gland. It involves several molecular mechanisms. The BRAF V600E mutation has been identified as the most common genetic abnormality in PTC. Moreover, it is known to be more prevalent in Korean PTC patients than in patients from other countries. We investigated distinct genetic profiles in Korean PTC through cDNA microarray analysis.
METHODS
Transcriptional profiles of five PTC samples and five paired normal thyroid tissue samples were generated using cDNA microarrays. The tumors were genotyped for BRAF mutations. The results of the cDNA microarray gene expression analysis were confirmed by real-time PCR and immunohistochemistry analysis of 35 PTC patients.
RESULTS
Four of the five patients whose PTC tissues were subjected to microarray analysis were found to carry the BRAF V600E mutation. Microarrays analysis of the five PTC tissue samples showed the expression of 96 genes to be increased and that of 16 genes decreased. Real-time reverse transcription-polymerase chain reaction (RT-PCR) confirmed increased expression of SLC34A2, TM7SF4, COMP, KLK7, and KCNJ2 and decreased expression of FOXA2, SLC4A4, LYVE-1, and TFCP2L1 in PTC compared with normal tissue. Of these genes, TFCP2L1, LYVE-1, and KLK7 were previously unidentified in PTC microarray analysis. Notably, Foxa2 activity in PTC was reduced, as shown by its cytoplasmic localization, in immunohistochemical analyses.
CONCLUSIONS
These findings demonstrate both similarities and differences between our results and previous reports. In Korean cases of PTC, Foxa2 activity was reduced with its cytoplasmic accumulation. Further studies are needed to confirm the relationship between FOXA2 and BRAF mutations in Korean cases of PTC.

Keyword

BRAF mutation; Oligonucleotide array sequence analysis; FOXA2 protein, human; Thyroid cancer

MeSH Terms

Adult
Aged
Carcinoma, Papillary/*genetics
Female
*Gene Expression Profiling
Hepatocyte Nuclear Factor 3-beta/analysis/genetics
Humans
Immunohistochemistry
Kallikreins/analysis/genetics
Korea
Male
Middle Aged
*Mutation
Oligonucleotide Array Sequence Analysis/*methods
Polymerase Chain Reaction
Proto-Oncogene Proteins B-raf/*genetics
Thyroid Neoplasms/*genetics
Vesicular Transport Proteins/analysis/genetics