42. Epigenomic profiling of anal cancer: does size matter? An RTOG 98-11 specimen study
Erin Siegel A , Steven Eschrich B , Kathryn Winter E , Bridget Riggs A , Anders Berglund B , Abidemi Ajidahun C , Jeff Simko F , Jaffer Ajani G , Anthony Magliocco D , Abul Elahi C , Domenico Coppola D and David Shibata CA Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
B Biomedical Informatics, Moffitt Cancer Center, Tampa, FL, USA.
C Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA.
D Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA.
E Department of Statistics, Radiation Therapy Oncology Group, Philadelphia, PA, USA.
F Biospecimen Resource, Radiation Therapy Oncology Group, San Francisco, CA, USA.
G MD Anderson Cancer Center, Houston, TX, USA.
Sexual Health 10(6) 590-590 https://doi.org/10.1071/SHv10n6ab42
Published: 22 November 2013
Abstract
Background: Anal cancer accounts for 4% of all lower gastrointestinal tract malignancies in the US. One of the most important predictors of prognosis among anal cancer patients is the size of the primary tumour. Tumours with diameters >5 cm have poorer disease-free survival than those with smaller tumours. Understanding the biological changes associated with tumour growth may provide information to guide therapy and improve patient outcomes. DNA methylation changes are critical epigenetic events in cancer development. Methods: In this study we sought to characterise the epigenomic signatures associated with anal cancer tumour size (≤5 cm vs >5 cm) in FFPE tissues from 121 patients (≤5 cm = 88; >5 cm = 33) who participated in the RTOG 98–11 cooperative group anal cancer clinical trial. Differential methylation, examined at >450 000 CpG loci using the Illumina Human Methylation 450 Array, were compared between the two groups using Mann–Whitney test (significance = P < 0.001 and difference in methylation β-value >0.1). Results: This study included 74 women and 47 men with a median age of 54 years. A total of 86 CpG loci were differentially methylated (78 increased and 8 decreased) in large vs small tumours. Genes harbouring CpG sites that were among the most highly differentially methylated included those associated with WNT signalling (FZD10, WNT9A), microRNAs (MIR200A) and novel methylated targets (PON3). Conclusions: These data provide evidence that epigenetic events likely play a significant role in the progression of anal SCC and may serve as biomarkers of prognosis. Similar epigenomic approaches may be useful at earlier stages of anal neoplastic progression for application in screening and early detection.
