Background: Hypomethylation of genomic DNA induces stem-cell properties in cancer cells and contributes to the treatment resistance of various malignancies. Objective: To examine the correlation between the methylation status of stem-cell-related genes and the treatment outcomes in patients with glioblastoma (GBM). Methods: The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between a group of patients with good prognosis (survival > 4 yr) and a group with poor prognosis (survival < 1 yr). Immunohistochemistry for proteins translated from hypomethylated genes, including alkaline phosphatase (ALPL), CD133, and CD44, was performed in 70 GBMs and 60 oligodendroglial tumors. Results: The genomic DNA in refractory GBM was more hypomethylated than in GBM from patients with relatively long survival (P = .0111). Stem-cell-related genes including ALPL, CD133, and CD44 were also significantly hypomethylated. A validation study using immunohistochemistry showed that DNA hypomethylation was strongly correlated with high protein expression of ALPL, CD133, and CD44. GBM patients with short survival showed high expression of these stem-cell markers. Multivariate analysis confirmed that co-expression of ALPL + CD133 or ALPL + CD44 was a strong predictor of short survival. Anaplastic oligodendroglial tumors without isocitrate dehydrogenase 1 mutation were significantly correlated with high ALPL expression and poor survival. Conclusion: Accumulation of stem-cell properties due to aberrant DNA hypomethylation is associated with the refractory nature of GBM.
Background: Hypomethylation of genomic DNA induces stem-cell properties in cancer cells and contributes to the treatment resistance of various malignancies. Objective: To examine the correlation between the methylation status of stem-cell-related genes and the treatment outcomes in patients with glioblastoma (GBM). Methods: The genome-wide DNA methylation status was determined using HumanMethylation450 BeadChips, and the methylation status was compared between a group of patients with good prognosis (survival > 4 yr) and a group with poor prognosis (survival < 1 yr). Immunohistochemistry for proteins translated from hypomethylated genes, including alkaline phosphatase (ALPL), CD133, and CD44, was performed in 70 GBMs and 60 oligodendroglial tumors. Results: The genomic DNA in refractory GBM was more hypomethylated than in GBM from patients with relatively long survival (P = .0111). Stem-cell-related genes including ALPL, CD133, and CD44 were also significantly hypomethylated. A validation study using immunohistochemistry showed that DNA hypomethylation was strongly correlated with high protein expression of ALPL, CD133, and CD44. GBM patients with short survival showed high expression of these stem-cell markers. Multivariate analysis confirmed that co-expression of ALPL + CD133 or ALPL + CD44 was a strong predictor of short survival. Anaplastic oligodendroglial tumors without isocitrate dehydrogenase 1 mutation were significantly correlated with high ALPL expression and poor survival. Conclusion: Accumulation of stem-cell properties due to aberrant DNA hypomethylation is associated with the refractory nature of GBM.
Authors: Eduardo Martinez; Neftali Vazquez; Alma Lopez; Victor Fanniel; Lilia Sanchez; Rebecca Marks; Leetoria Hinojosa; Victoria Cuello; Marisa Cuevas; Angelica Rodriguez; Cerin Tomson; Andrea Salinas; Mark Abad; Martin Holguin; Noel Garza; Abraham Arenas; Kevin Abraham; Luis Maldonado; Vivian Rojas; Alex Basdeo; Erin Schuenzel; Michael Persans; Wendy Innis-Whitehouse; Megan Keniry Journal: J Cancer Res Clin Oncol Date: 2020-02-06 Impact factor: 4.553
Authors: W Dai; H Liu; Y Liu; X Xu; D Qian; S Luo; E Cho; D Zhu; C I Amos; S Fang; J E Lee; X Li; H Nan; C Li; Q Wei Journal: Br J Dermatol Date: 2020-02-26 Impact factor: 9.302
Authors: Alexandra McAleenan; Claire Kelly; Francesca Spiga; Ashleigh Kernohan; Hung-Yuan Cheng; Sarah Dawson; Lena Schmidt; Tomos Robinson; Sebastian Brandner; Claire L Faulkner; Christopher Wragg; Sarah Jefferies; Amy Howell; Luke Vale; Julian P T Higgins; Kathreena M Kurian Journal: Cochrane Database Syst Rev Date: 2021-03-12