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Tumor Biology

, Volume 37, Issue 9, pp 12609–12618 | Cite as

Aberrant DNA methylation of acute myeloid leukemia and colorectal cancer in a Chinese pedigree with a MLL3 germline mutation

  • Fuhua Yang
  • Qiang Gong
  • Wentao Shi
  • Yunding Zou
  • Jingmin Shi
  • Fengjiang Wei
  • Qingrong Li
  • Jieping Chen
  • Wei-Dong Li
Original Article

Abstract

Unlike genetic aberrations, epigenetic alterations do not modify the deoxyribonucleic acid (DNA) coding sequence and can be reversed pharmacologically. Identifying a particular epigenetic alteration such as abnormal DNA methylation may provide better understanding of cancers and improve current therapy. In a Chinese pedigree with colorectal carcinoma and acute myeloid leukemia, we examined the genome-wide DNA methylation level of cases and explored the role of methylation in pathogenesis and progression. DNA methylation status in the four cases, which all harbor a MLL3 germline mutation, differed from that of the normal control, and hypermethylation was more prevalent. Also, more CpG sites were hypermethylated in the acute-phase AML patient than in the AML patient in remission. Fifty-nine hyper- or hypomethylated genes were identified as common to all four cases. Genome-wide DNA methylation analysis demonstrated that differentially methylated sites among acute myeloid leukemia and colorectal carcinoma cases and the control were in both promoters (CpG island) and gene body regions (shelf/shore areas). Hypermethylation was more prevalent in cancer cases. The study supports the suggestion that the level of DNA methylation changes in AML progression.

Keywords

Acute myeloid leukemia Colorectal cancer DNA methylation 

Notes

Acknowledgments

We thank all subjects who donated blood samples for genetic research purposes. This work was supported in part by grant 81070576 from the National Natural Science Foundation of China and grant 12JCZDJC24700 from Tianjin Municipal Science and Technology Commission to W.-D.L.; and by National Natural Science Foundation of China (NSFC 81270605,30971066,81470324), Third Military Medical University Clinical and Science Great Fund Project (2102XLC03), Chongqing Postgraduate Education Reform Project (yjg123114), Chongqing Natural Science Fund Project (CSTC’2008BA5001), and Military Emphasis Medical Scientific Research Project Fund to J.-P.C.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2016_5130_MOESM1_ESM.docx (12 kb)
Supplement table 1 (DOCX 11 kb)
13277_2016_5130_MOESM2_ESM.docx (14 kb)
Supplement table 2 (DOCX 13 kb)
13277_2016_5130_MOESM3_ESM.docx (18 kb)
Supplement table 3 (DOCX 18 kb)
13277_2016_5130_Fig6_ESM.gif (29 kb)
Supplement figure 1

Differentially methylated sites at enhancers. (GIF 29 kb)

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High resolution image (TIFF 7978 kb)
13277_2016_5130_Fig7_ESM.gif (188 kb)
Supplement figure 2

Association between the hypermethylated CpG sites and the expression levels of their respective genes in AML cases from the TCGA database. Data are presented as linear regression (solid straight line) graph and 95 % confidence interval (dotted line). (A) cg05995465 and HDAC4; (B) cg08466517 and TNIP3; (C) cg06758191 and AFAP1; (D)cg17704839 and UBL5. (GIF 187 kb)

13277_2016_5130_MOESM5_ESM.tif (40.7 mb)
High resolution image (TIFF 41668 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Fuhua Yang
    • 1
  • Qiang Gong
    • 2
  • Wentao Shi
    • 1
  • Yunding Zou
    • 2
  • Jingmin Shi
    • 1
  • Fengjiang Wei
    • 1
  • Qingrong Li
    • 2
  • Jieping Chen
    • 2
  • Wei-Dong Li
    • 1
  1. 1.Research Center of Basic Medical SciencesTianjin Medical UniversityTianjinChina
  2. 2.Department of HematologySouthwest Hospital, Third Military Medical UniversityChongqingChina

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