Human T-cell leukemia virus type I (HTLV-I) is associated with fatal lymphoproliferative disorders known as adult T-cell leukemia/lymphoma (ATL) [
1,
2]. The disease is classified into distinct subtypes - smoldering, chronic, acute and lymphoma - that differ in their clinical presentation and in their response to treatment [
3]. Since the clinical subtypes of ATL have distinct genomic alterations and different clinical progression, these diseases require a different approach for treatment [
4]. However, current therapies for ATL do not result in long-term remission and even the clinically less aggressive forms ultimately evolve to the acute. The 4 year survival rate for acute-, lymphoma-, chronic- and smoldering-type ATL is 11, 16, 36, and 52 %, respectively [
5,
6]. The viral oncoprotein Tax plays an important role in initiation of events leading to cellular transformation [
7,
8]. However, the fact that the disease has a low penetrance and is observed after a long latency period of several decades has led to the hypothesis that the virus initiates oncogenic events but is not sufficient for cellular transformation [
9,
10]. In support of this notion epigenetic alterations are required for the development of ATL. Promoter hyper-methylation associated with loss of SHP1 expression coincides with the IL-2-independent transformation of T cells by HTLV-I in vitro [
11]. SHP1 is one of the most frequently altered genes in ATL patients, with an overall hyper-methylation rate of 90 % [
12]; other tumor suppressor genes inactivated by methylation in ATL include p53-related p73, CDKN2A and p21CIP1/WAF1 [
13]. The fact that histone methyl-transferase EZH2 has been demonstrated to repress p57KIP2 expression through histone H3 lysine 27 trimethylation (H3K27me3) [
14], and that p57KIP2 is methylated in nearly 50 % of newly diagnosed ALL patients [
15], prompted us to analyze the status of cellular genes involved in chromatin silencing. In this study we use next generation sequencing (NGS) to characterize the genetic mutations in EZH1, EZH2, EED, SUZ12, DNMT1, DNMT3A, DNMT3B, TET1, TET2, TET3, IDH1/2, MLL, MLL2, MLL3, MLL4 and ASXL1. Our study revealed a high frequency of mutation in epigenetic regulators in ATL samples, suggesting that chromatin remodeling by some of these genes may play a role in the pathogenesis of ATL.