Myopodin Methylation is Associated With Clinical Outcome in Patients With T1G3 Bladder Cancer

Abstract

Epigenetic analysis revealed that myopodin methylation was associated with tumor aggressiveness and clinical outcome in patients with T1G3 disease. Myopodin methylation distinguished patients responding to bacillus Calmette-Guerin from those who may require a more aggressive therapeutic approach.

Comprehensive Genome Methylation Analysis in Bladder Cancer: Identification and Validation of Novel Methylated Genes and Application of These as Urinary Tumor Markers

“…Several groups have reported methylation markers of progression (14,20,23,24,41,42). We identified and validated TBX4 as a promising candidate of disease progression, but in addition to TBX4, we also found markers reported previously.…”

Epigenetik Değişiklikler ve Mesane Kanseri Arasındaki İlişki

“…Başka bir çalışmada TIMP-3 metilasyonun hastalığın progresyonu ve hasta prognozu ile ilişkili olduğu bulunmuştur (45). Literatürde CDH-1, RASSF1A gibi genlerdeki hipermetilasyonun yüksek tümör sınıfı ile APAF-1, IGFBP3, p16 INK4A , p14 ARF metilasyonunun tümör rekürrensi ile RUNX-3, Myopodin metilasyonunun da tümör progresyonu ile ilişkili olabileceği gösterilmiştir (46,47,48,49,50,51). Bir başka tümör süpresör gen olan ITIH-5'in promoter hipermetilasyonunun, ITIH-5 mRNA down regülasyonuna yol açarak özellikle pT1 tümörlerde erken relaps ve progresyon ile ilişkili olduğu gösterilmiştir (52).…”

Hypermethylation in bladder cancer: biological pathways and translational applications

“…In the last few years, several genes have been shown to be hypermethylated and play a tumor suppressor role in bladder cancer, roles which have not been fully characterized in this disease to date. These include fine analyses of genomic regions being hypermethylated [56,128], and individual tumor suppresor candidates such as the Runt-related transcription factor 3 gene (RUNX3) [100,[129][130][131][132], myopodin, a cytoskeleton actin binding protein whose methylation was found useful to predict BCG response [133][134][135], the phosphatase and tensin homolog gene (PTEN) [58][59][60]130], the hypermethylated in cancer 1 gene (HIC1) [86,87,130], the Von Hippel-Lindau tumor suppresor gene (VHL) [58,59,68], the Wilms tumor 1 gene (WT1) [59,60], the deleted in bladder cancer,chromosomal region candidate 1 gene (DBCCR1) [128], the immunoglobulin superfamily member 4 gene (IGSF4) [58,59,91], or the deleted in breast cancer 1 gene (DBC1) [140]. Differentiation related genes have also been found methylated with high prevalence in bladder tumors such as the S-100 family of proteins [136], the Sry-related-hmg box 9 gene (SOX9) [47], the polyamine modulated factor 1 gene (PMF1) [137], the cancer antigen 1 gene (CAGE1) [130,138], the estrogen receptor gene (ESR1) [58][59][60]87], or the retinoic acid receptor gene (RARB) [58,…”

“…An increasing number of hypermethylation individual events at single gene loci are indicating differential outcomes among bladder cancer patients. Among the genes most frequently studied, for example, hypermethylation of the genes encoding such as CDKN2A [72,73,78], DAPK [68,72,97,98], RASFF1A [72,73,86,115], CDH1 [72,73,86,95], SFRPs [123,125], RUNX3 [129,132], or myopodin [134,135], among others, has strongly been linked to poor outcomes in tissue specimens (Table 1) [34][35][36][37][38][39][40]. Combinations of tumor-suppressor genes have also been utilized for this purpose [58,59].…”