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Hypermethylation of the DNA mismatch repair gene hMLH1 and Its association with lymph node metastasis and T1799A BRAF mutation in patients with papillary thyroid cancer
Version of Record online: 9 MAY 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 2, pages 247–255, 15 July 2008
How to Cite
Guan, H., Ji, M., Hou, P., Liu, Z., Wang, C., Shan, Z., Teng, W. and Xing, M. (2008), Hypermethylation of the DNA mismatch repair gene hMLH1 and Its association with lymph node metastasis and T1799A BRAF mutation in patients with papillary thyroid cancer. Cancer, 113: 247–255. doi: 10.1002/cncr.23548
- Issue online: 8 JUL 2008
- Version of Record online: 9 MAY 2008
- Manuscript Accepted: 4 MAR 2008
- Manuscript Revised: 19 FEB 2008
- Manuscript Received: 7 DEC 2007
- American Cancer Society Research Scholar Grant. Grant Number: RSG 05-199-01-CCE
- Thyroid, Head And Neck Cancer (THANC) Foundation
- DNA repair genes;
- BRAF mutation;
- thyroid cancer
It remains to be investigated whether the aberrant methylation of DNA repair genes plays a pathogenic role in BRAF mutation-promoted tumorigenesis of papillary thyroid cancer (PTC).
In the current study, the promoter methylation status of 23 DNA repair genes in relation to clinicopathologic characteristics and BRAF mutation was examined in PTC tumors using methylation-specific polymerase chain reaction.
Among the 38 PTC tumors examined, 3 of 23 DNA repair genes were hypermethylated, including the hMLH1 gene in 8 of 38 samples (21%), the PCNA gene in 5 of 38 samples (13%), and the OGG1 gene in 2 of 38 samples (5%). Methylation of these genes was also found in some thyroid cancer cell lines. Methylation of the hMLH1 gene in particular was found to be associated with lymph node metastasis of PTC (5 of 8 samples [63%] in the methylation group vs 3 of 30 samples [10%] in the nonmethylation group; P = .0049). Methylation of the hMLH1 gene was also found to be associated with the T1799A BRAF mutation in PTC (6 of 19 samples (32%) in the BRAF mutation-positive group vs 2 of 19 samples (11%) in the BRAF mutation-negative group; P = .042).
The data from the current study suggest that, as shown previously in colon cancer, aberrant methylation of the hMLH1 gene may play a role in BRAF mutation-promoted thyroid tumorigenesis. Cancer 2008. © 2008 American Cancer Society.