Distinction of acute lymphoblastic leukemia from acute myeloid leukemia through microarray-based DNA methylation analysis

Patterns of DNA methylation are substantially altered in malignancies compared to normal tissue, with both genome-wide hypomethylation and regional increase of cytosine methylation at dinucleotides of cytosine and guanine, i.e., CpG dinucleotides. While genome-wide hypomethylation renders chromosomes instable, hypermethylation of CpGs in promoter regions is generally associated with transcriptional silencing, e.g., of tumor suppressor genes. To investigate whether disease-specific methylation profiles exist for different entities of acute leukemia, a microarray-based DNA methylation analysis simultaneously assessing 249 CpG dinucleotides originating from 57 genes was employed. Hereby, samples from precursor B-cell acute lymphoblastic leukemia (ALL) could be distinguished from cases of acute myeloid leukemia by virtue of N33, EGR4, CDC2, CCND2, or MOS hypermethylation in ALL.

[1]  Hung D. Nguyen,et al.  DNA methylation differences associated with tumor tissues identified by genome scanning analysis. , 1998, Genomics.

[2]  J. Nyce.  Drug-induced DNA hypermethylation and drug resistance in human tumors. , 1989, Cancer research.

[3]  S. Clark,et al.  High sensitivity mapping of methylated cytosines. , 1994, Nucleic acids research.

[4]  S. Baylin,et al.  Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. , 1999, Cancer research.

[5]  Thomas D. Otto,et al.  Tumour class prediction and discovery by microarray-based DNA methylation analysis , 2002 .

[6]  S. Baylin,et al.  Concordant methylation of the ER and N33 genes in glioblastoma multiforme , 1998, Oncogene.

[7]  M. Link,et al.  Frequent and selective methylation of p15 and deletion of both p15 and p16 in T-cell acute lymphoblastic leukemia. , 1997, Cancer research.

[8]  Matty P. Weijenberg,et al.  A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer , 2002, Nature Genetics.

[9]  M. Kitajima,et al.  Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences , 2002, Oncogene.

[10]  J. Shaffer.  Multiple Hypothesis Testing , 1995 .

[11]  G. Peters,et al.  Expression of cyclin D2 in Epstein-Barr virus-positive Burkitt's lymphoma cell lines is related to methylation status of the gene , 1995, Journal of virology.

[12]  Ross Ihaka,et al.  Gentleman R: R: A language for data analysis and graphics , 1996 .

[13]  Peter A. Jones,et al.  The fundamental role of epigenetic events in cancer , 2002, Nature Reviews Genetics.

[14]  M. Rugge,et al.  Fez1/lzts1 alterations in gastric carcinoma. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  P. Malfertheiner,et al.  Absence of cyclin D2 expression is associated with promoter hypermethylation in gastric cancer , 2003, British Journal of Cancer.

[16]  D. Hossfeld.  E.S. Jaffe, N.L. Harris, H. Stein, J.W. Vardiman (eds). World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues , 2002 .

[17]  C. Bartram,et al.  Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation. , 1999, Blood.

[18]  S. Weitzman,et al.  Loss of cyclin D2 expression in the majority of breast cancers is associated with promoter hypermethylation. , 2001, Cancer research.

[19]  S. Baylin,et al.  HIC1 hypermethylation is a late event in hematopoietic neoplasms. , 1997, Cancer research.

[20]  Peter A. Jones,et al.  Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment. , 2002, Blood.

[21]  Hypermethylation of E-cadherin in leukemia. , 2000 .

[22]  R. Parwaresch,et al.  Cell lineage specificity in G-CSF receptor gene methylation , 1999, Leukemia.

[23]  T. Huang,et al.  Methylation profiling of CpG islands in human breast cancer cells. , 1999, Human molecular genetics.

[24]  Huidong Shi,et al.  The androgen receptor gene is preferentially hypermethylated in follicular non-Hodgkin's lymphomas. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  W. Isaacs,et al.  Structure and methylation-associated silencing of a gene within a homozygously deleted region of human chromosome band 8p22. , 1996, Genomics.

[26]  K. Makar,et al.  Epigenetic regulation of T cell fate and function. , 2002, The Journal of infectious diseases.

[27]  J. Herman,et al.  Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. , 1996, Cancer research.

[28]  G. Liang,et al.  Relationship between transcription and DNA methylation. , 2000, Current topics in microbiology and immunology.

[29]  J. Herman,et al.  Distinct patterns of inactivation of p15INK4B and p16INK4A characterize the major types of hematological malignancies. , 1997, Cancer research.

[30]  A. Razin,et al.  DNA methylation and gene expression , 1991, Microbiological reviews.

[31]  A. Bird,et al.  Methylation-Induced Repression— Belts, Braces, and Chromatin , 1999, Cell.

[32]  M. Caligiuri,et al.  Aberrant CpG-island methylation has non-random and tumour-type–specific patterns , 2000, Nature Genetics.

[33]  J. Herman,et al.  A gene hypermethylation profile of human cancer. , 2001, Cancer research.

[34]  M. Toyota,et al.  Methylation profiling in acute myeloid leukemia. , 2001, Blood.

[35]  L. V. D. Heuvel,et al.  DNA methylation patterns in the calcitonin gene region at first diagnosis and at relapse of acute lymphoblastic leukemia (ALL) , 1997, Leukemia.

[36]  H. Gralnick,et al.  Proposals for the Classification of the Acute Leukaemias French‐American‐British (FAB) Co‐operative Group , 1976, British journal of haematology.

[37]  R. Hruban,et al.  Methylation of cyclin D2 is observed frequently in pancreatic cancer but is also an age-related phenomenon in gastrointestinal tissues. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[38]  J. Herman,et al.  Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation. , 1999, Cancer research.

[39]  S. Clark,et al.  Detection and measurement of PCR bias in quantitative methylation analysis of bisulphite-treated DNA. , 1997, Nucleic acids research.

[40]  K. Ohshima,et al.  Hypomethylation status of CpG sites at the promoter region and overexpression of the human MDR1 gene in acute myeloid leukemias. , 1998, Blood.

[41]  G. V. Vande Woude,et al.  Synergy between the Mos/mitogen-activated protein kinase pathway and loss of p53 function in transformation and chromosome instability , 1997, Molecular and cellular biology.

[42]  Hansjuerg Alder,et al.  FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[43]  A. Olek,et al.  A modified and improved method for bisulphite based cytosine methylation analysis. , 1996, Nucleic acids research.

[44]  J. Baraban,et al.  The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience , 1999, Trends in Neurosciences.

[45]  S. Baylin,et al.  The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. , 1996, Cancer research.

[46]  J. Herman,et al.  CpG island methylator phenotype in colorectal cancer. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[47]  J. Herman,et al.  p15(INK4B) CpG island methylation in primary acute leukemia is heterogeneous and suggests density as a critical factor for transcriptional silencing. , 1999, Blood.

[48]  T. Coleman,et al.  Cdc2 regulatory factors. , 1994, Current opinion in cell biology.

[49]  Rachel Jones,et al.  Behavioural genetics: Worms gang up on bacteria , 2002, Nature Reviews Genetics.