CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma.
Thyroid
; 16(7): 633-42, 2006 Jul.
Article
en En
| MEDLINE
| ID: mdl-16889486
ABSTRACT
OBJECTIVE:
To understand the role of epigenetic inactivation of tumor-related genes in the pathogenesis of thyroid cancer, we investigated the methylation profile of distinct thyroid neoplasms.DESIGN:
We analyzed the methylation pattern of 17 gene promoters in nine thyroid cancer cell lines and in 38 primary thyroid carcinomas (13 papillary thyroid carcinoma [PTC], 10 follicular thyroid carcinoma [FTC], 9 undifferentiated thyroid carcinoma [UTC], 6 medullary thyroid carcinoma [MTC]), 12 goiters, and 10 follicular adenomas (FA) by methylation- specific polymerase chain reaction (PCR). Epigenetic inactivation was validated by expression analysis. MAINOUTCOME:
Twelve of these genes (RASSF1A, p16(INK4A), TSHR, MGMT, DAPK, ERalpha, ERbeta, RARbeta, PTEN, CD26, SLC5A8, and UCHL1) were frequently methylated in UTC (15%-86%) and thyroid cancer cell lines (25%-100%). In the more aggressive UTC, the mean methylation index (MI = 0.44) was the highest compared to other thyroid alterations PTC (MI = 0.29, p = 0.123), FTC (MI = 0.15, p = 0.005), MTC (MI = 0.13; p = 0.017), FA (MI = 0.27; p = 0.075) and goiters (MI = 0.23; p = 0.024). Methylation of TSHR, MGMT, UCHL1, and p16 occurred preferentially in UTC and this inactivation was reverted by a demethylating agent.CONCLUSIONS:
Our results show that hypermethylation of several tumor-related gene promoters is a frequent event in UTC. The hypermethylation status may be reversed by DNA demethylating agents. Their clinical value remains to be investigated.
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Tiroides
/
Carcinoma
/
Regulación Neoplásica de la Expresión Génica
/
Islas de CpG
/
Metilación de ADN
Límite:
Humans
Idioma:
En
Año:
2006
Tipo del documento:
Article