PubMed 23571109

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv10.1 , Kv11.1

Title: Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel.

Authors: Mine S Cicek, Devin C Koestler, Brooke L Fridley, Kimberly R Kalli, Sebastian M Armasu, Melissa C Larson, Chen Wang, Stacey J Winham, Robert A Vierkant, David N Rider, Matthew S Block, Brandy Klotzle, Gottfried Konecny, Boris J Winterhoff, Habib Hamidi, Viji Shridhar, Jian-Bing Fan, Daniel W Visscher, Janet E Olson, Lynn C Hartmann, Marina Bibikova, Jeremy Chien, Julie M Cunningham, Ellen L Goode

Journal, date & volume: Hum. Mol. Genet., 2013 Aug 1 , 22, 3038-47

PubMed link:

Ovarian cancer remains the leading cause of death in women with gynecologic malignancies, despite surgical advances and the development of more effective chemotherapeutics. As increasing evidence indicates that clear-cell ovarian cancer may have unique pathogenesis, further understanding of molecular features may enable us to begin to understand the underlying biology and histology-specific information for improved outcomes. To study epigenetics in clear-cell ovarian cancer, fresh frozen tumor DNA (n = 485) was assayed on Illumina Infinium HumanMethylation450 BeadChips. We identified a clear-cell ovarian cancer tumor methylation profile (n = 163) which we validated in two independent replication sets (set 1, n = 163; set 2, n = 159), highlighting 22 CpG loci associated with nine genes (VWA1, FOXP1, FGFRL1, LINC00340, KCNH2, ANK1, ATXN2, NDRG21 and SLC16A11). Nearly all of the differentially methylated CpGs showed a propensity toward hypermethylation among clear-cell cases. Several loci methylation inversely correlated with tumor gene expression, most notably KCNH2 (HERG, a potassium channel) (P = 9.5 × 10(-7)), indicating epigenetic silencing. In addition, a predicted methylation class mainly represented by the clear-cell cases (20 clear cell out of 23 cases) had improved survival time. Although these analyses included only 30 clear-cell carcinomas, results suggest that loss of expression of KCNH2 (HERG) by methylation could be a good prognostic marker, given that overexpression of the potassium (K(+)) channel Eag family members promotes increased proliferation and results in poor prognosis. Validation in a bigger cohort of clear-cell tumors of the ovary is warranted.