Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation

• Published in: Clinical oncology (Royal College of Radiologists (Great Britain)) 2015-12, Vol.27 (12), p.720-727
• Main Authors: Sood, S, Patel, F.D, Ghosh, S, Arora, A, Dhaliwal, L.K, Srinivasan, R
• Format: Article
• Language: English
• Subjects: Adult; Aged; Chemoradiation; Chemoradiotherapy; DNA Methylation; Epigenesis, Genetic - genetics; ESR1; Estrogen Receptor alpha - genetics; Female; Gene Expression Regulation, Neoplastic; gene promoter methylation; Hematology, Oncology and Palliative Medicine; hTERT; Humans; invasive cervical carcinoma; Middle Aged; MyoD Protein - genetics; MYOD1; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Promoter Regions, Genetic - genetics; Radiology; Telomerase - genetics; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - therapy
• ISSN: 0936-6555; 1433-2981
• DOI: 10.1016/j.clon.2015.08.001

Abstract Aims Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. Materials and methods In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. Results The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. Conclusion Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy.