CpG island methylator phenotype predicts progression of malignant melanoma.
CpG island methylator phenotype predicts progression of malignant melanoma.
复制标题
DOI：
10.1158/1078-0432.ccr-08-1361
复制
发表时间：
2009-03-01
期刊：
影响因子：
--
通讯作者：
Hoon DS
中科院分区：
文献类型：
--
作者：
Tanemura A;Terando AM;Sim MS;van Hoesel AQ;de Maat MF;Morton DL;Hoon DS
The CpG island methylator phenotype (CIMP) may be associated with development of malignancy through coordinated inactivation of tumor suppressor and tumor-related genes (TRG) and methylation of multiple noncoding, methylated-in-tumor (MINT) loci. These epigenetic changes create a distinct CIMP pattern that has been linked to recurrence and survival in gastrointestinal cancers. Because epigenetic inactivation of TRGs also has been shown in malignant melanoma, we hypothesized the existence of a clinically significant CIMP in cutaneous melanoma progression. The methylation status of the CpG island promoter region of TRGs related to melanoma pathophysiology (WIF1, TFPI2, RASSF1A, RARβ2, SOCS1, and GATA4) and a panel of MINT loci (MINT1, MINT2, MINT3, MINT12, MINT17, MINT25, and MINT31) in primary and metastatic tumors of different clinical stages (n = 122) was assessed. Here, we show an increase in hypermethylation of theTRGsWIF1,TFPI2, RASSF1A, and SOCS1with advancing clinical tumor stage. Furthermore, we find a significant positive association between the methylation status of MINT17, MINT31, and TRGs. The methylation status of MINT31is associated with disease outcome in stage III melanoma. These findings show the significance of a CIMP pattern that is associated with advancing clinical stage of malignant melanoma. Future prospective large-scale studies may determine if CIMP-positive primary melanomas are at high risk of metastasis or recurrence.
