Aberrant DNA methylation of apoptotic signaling genes in patients responsive and nonresponsive to therapy for cervical carcinoma.

Abstract

OBJECTIVE:

We sought to investigate CpG-island methylation profiling of apoptotic genes apoptotic protease activating factor 1, caspase 8, death-associated protein kinase (DAPK), tumor necrosis factor receptor superfamily member 6 (FAS), Survivin, and tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and its role in resistance to therapy in cervical cancer (CXCA).

STUDY DESIGN:

Methylation status was performed in 85 CXCA patients comprising therapeutic nonresponses and responses using methylation-specific polymerase chain reaction.

RESULTS:

Methylation frequency of DAPK and FAS showed a statistically significant difference between therapeutic nonresponses and responses. Concurrent methylation of multiple apoptotic genes was a preferential event in CXCA. Moreover, concerted methylation of pair genes was observed in DAPK, FAS, and tumor necrosis factor-related apoptosis-inducing ligand receptor-1 and found only in nonresponses.

CONCLUSION:

Aberrant methylation of apoptotic signaling genes results in acquired resistance to therapy. Detection of methylation in apoptotic signaling genes is potentially useful as a molecular predictive marker for strategic planning of treatment efficacy and evaluation of therapeutic outcome in CXCA, leading to an improvement of patients' survival.

• Authors: Patimaporn Chaopatchayakul, Patcharee Jearanaikoon, Pissamai Yuenyao, Temduang Limpaiboon
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 202 Issue 3 Pg. 281.e1-9 (Mar 2010) ISSN: 1097-6868 [Electronic] United States
• PMID: 20117760 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Mosby, Inc. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Apoptotic Protease-Activating Factor 1
• BIRC5 protein, human
• Genetic Markers
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor
• Survivin
• TNFRSF10A protein, human
• fas Receptor
• Death-Associated Protein Kinases
• Calcium-Calmodulin-Dependent Protein Kinases
• CASP8 protein, human
• Caspase 8

Topics

• Adenocarcinoma (drug therapy, genetics, pathology)
• Apoptosis Regulatory Proteins (genetics)
• Apoptotic Protease-Activating Factor 1 (genetics)
• Calcium-Calmodulin-Dependent Protein Kinases (genetics)
• Carcinoma, Squamous Cell (genetics, pathology, therapy)
• Caspase 8 (genetics)
• DNA Methylation (genetics)
• Death-Associated Protein Kinases
• Drug Resistance, Neoplasm (genetics)
• Female
• Genetic Markers
• Humans
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins (genetics)
• Polymerase Chain Reaction
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor (genetics)
• Survivin
• Treatment Failure
• Uterine Cervical Neoplasms (genetics, pathology, therapy)
• fas Receptor (genetics)