Project B1

Epigenetic Profiling of Human Hepatocellular Carcinoma

Principal Investigators: Prof. Dr. Ulrich Lehmann, Prof. Dr. Hans Kreipe


Short Summary

 Using state-of-the-art DNA methylation analysis technology we will determine which sets of genes are affected in different types, grades and etiologic backgrounds of hepatocellular cancer. Analog to studies on in hemochromatosis we will investigate whether the causative agent of liver cell damage leading to cancer causes a specific methylation signature. The methylation analysis will focus on the identification of differentially methylated regions regulating the expression of microRNA genes. Detailed sequence analyses and functional assays will be employed for further characterization of these differentially methylated regions.



List of relevant publications

  1. Lehmann U, Hasemeier B, Christgen M, Muller M, Romermann D, Langer F, Kreipe H (2008) Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J Pathol 214:17-24.
  2. Romermann D, Hasemeier B, Metzig K, Gohring G, Schlegelberger B, Langer F, Kreipe H, Lehmann U (2008) Global increase in DNA methylation in patients with myelodysplastic syndrome. Leukemia 22:1954-1956.
  3. Hasemeier B, Christgen M, Kreipe H, Lehmann U (2008) Reliable microRNA profiling in routinely processed formalin-fixed paraffin-embedded breast cancer specimens using fluorescence labelled bead technology. BMC Biotechnol 8:90.
  4. Christgen M, Bruchhardt H, Ballmaier M, Krech T, Langer F, Kreipe H, Lehmann U (2008) KAI1/CD82 is a novel target of estrogen receptor-mediated gene repression and downregulated in primary human breast cancer. Int J Cancer 123:2239-46.
  5. Lehmann U, Wingen LU, Brakensiek K, Wedemeyer H, Becker T, Heim A, Metzig K, Hasemeier B, Kreipe H, Flemming P (2007) Epigenetic defects of hepatocellular carcinoma are already found in non-neoplastic liver cells from patients with hereditary haemochromatosis. Hum Mol Genet 16:1335-42.
  6. Brakensiek K, Wingen LU, Langer F, Kreipe H, Lehmann U (2007) Quantitative High-Resolution CpG Island Mapping with Pyrosequencing Reveals Disease-Specific Methylation Patterns of the CDKN2B Gene in Myelodysplastic Syndrome and Myeloid Leukemia. Clin Chem 53:17-23.
  7. Lehmann U, Berg-Ribbe I, Wingen LU, Brakensiek K, Becker T, Klempnauer J, Schlegelberger B, Kreipe H, Flemming P (2005) Distinct methylation patterns of benign and malignant liver tumors revealed by quantitative methylation profiling. Clin Cancer Res 11:3654-60.
  8. Tessema M, Langer F, Bock O, Seltsam A, Metzig K, Hasemeier B, Kreipe H, Lehmann U (2005) Down-regulation of the IGF-2/H19 locus during normal and malignant hematopoiesis is independent of the imprinting pattern. Int J Oncol 26:499-507.
  9. Brakensiek K, Langer F, Kreipe H, Lehmann U (2005) Absence of p21(CIP 1), p27(KIP 1) and p 57(KIP 2) methylation in MDS and AML. Leuk Res 29:1357-60.
  10. Brakensiek K, Langer F, Schlegelberger B, Kreipe H, Lehmann U (2005) Hypermethylation of the suppressor of cytokine signalling-1 (SOCS-1) in myelodysplastic syndrome. Br J Haematol 130:209-17.
  11. Länger F, Dingemann J, Kreipe H, Lehmann U (2005) Up-regulation of DNA methyltransferases DNMT1, 3A, and 3B in myelodysplastic syndrome. Leuk Res 29:325-29.
  12. Brakensiek K, Langer F, Kreipe H, Lehmann U (2004) Low level of DAP-kinase DNA methylation in myelodysplastic syndrome. Blood 104:1586-87.
  13. Tessema M, Langer F, Dingemann J, Ganser A, Kreipe H, Lehmann U (2003) Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML). Leukemia 17:910-18.
  14. Lehmann U, Celikkaya G, Hasemeier B, Langer F, Kreipe, H (2002) Promoter hypermethylation of the death-associated protein kinase gene in breast cancer is associated with the invasive lobular subtype. Cancer Res 62:6634-38.
  15. Lehmann U, Langer F, Feist H, Glockner S, Hasemeier B, Kreipe H (2002) Quantitative assessment of promoter hypermethylation during breast cancer development. Am J Pathol 160:605-12.
  16. Lehmann U, Hasemeier B, Lilischkis R, Kreipe H (2001) Quantitative analysis of promoter hypermethylation in laser-microdissected archival specimens. Lab Invest  81:635-38.
  17. Lehmann U, Kreipe H (2001) Real-time PCR-based assay for quantitative determination of methylation status. Methods Mol Biol 287:207-18.



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