Daniel Römermann

Publications of Daniel Römermann

• Epigenetic inactivation of tumour suppressor gene KLF11 in myelodysplastic syndromes*

  Authors: Anna Potapova, Britta Hasemeier, Daniel Römermann, Kathleen Metzig, Gudrun Göhring, Brigitte Schlegelberger, Florian Länger, Hans Kreipe, Ulrich Lehmann

  European journal of haematology. 11/2009;

  Abstract The identification of aberrantly hypermethylated genes may lead to the development of new diagnostic markers and the identification of novel targets of epigenetic therapy in myelodysplasticAbstract The identification of aberrantly hypermethylated genes may lead to the development of new diagnostic markers and the identification of novel targets of epigenetic therapy in myelodysplastic syndromes (MDS). We therefore investigated the methylation status of transcription factor genes KLF5, KLF11, and MAFB, shown to be aberrantly methylated in myelogeneous leukaemia cells, in a series of 115 myelodysplastic syndromes patient as well as in 25 control subjects. Using quantitative high-resolution pyrosequencing methodology KLF11, MAFB, and KLF5 were shown for the first time to be hypermethylated in 17 (15%), 8 (7%), and 2 (1.7%) cases, respectively, but not in any of the patients with an isolated 5q-deletion. Patient samples harboring KLF11 methylation displayed reduced KLF11 mRNA expression and KLF11 hypermethylation correlated with a high IPSS score (p < 0.05). In conclusion, epigenetic inactivation and subsequent transcriptional repression of the KLF11 gene is quite frequent in myelodysplastic syndromes. Patients with an isolated 5q-deletion seem to harbour a distinct epigenetic profile.

• Comprehensive genetic and functional characterization of IPH-926: a novel CDH1-null tumour cell line from human lobular breast cancer.

  Authors: Matthias Christgen, Henriette Bruchhardt, Catarina Hadamitzky, Cornelia Rudolph, Doris Steinemann, Dorothea Gadzicki, Britta Hasemeier, Daniel Römermann, Tim Focken, Till Krech, Matthias Ballmaier, Brigitte Schlegelberger, Hans Kreipe, Ulrich Lehmann

  The Journal of pathology. 11/2008;

  Infiltrating lobular breast cancer (ILBC) is a clinically and biologically distinct tumour entity defined by a characteristic linear cord invasion pattern and inactivation of the CDH1 tumourInfiltrating lobular breast cancer (ILBC) is a clinically and biologically distinct tumour entity defined by a characteristic linear cord invasion pattern and inactivation of the CDH1 tumour suppressor gene encoding for E-cadherin. ILBCs also lack beta-catenin expression and show aberrant cytoplasmic localization of the E-cadherin binding protein p120-catenin. The lack of a well-characterized ILBC cell line has hampered the functional characterization of ILBC cells in vitro. We report the establishment of a permanent ILBC cell line, named IPH-926, which was derived from a patient with metastatic ILBC. The DNA fingerprint of IPH-926 verified genetic identity with the patient and had no match among the human cell line collections of several international biological resource banks. IPH-926 expressed various epithelial cell markers but lacked expression of E-cadherin due to a previously unreported, homozygous CDH1 241ins4 frameshift mutation. Detection of the same CDH1 241ins4 mutation in archival tumour tissue of the corresponding primary ILBC proved the clonal origin of IPH-926 from this particular tumour. IPH-926 also lacked beta-catenin expression and showed aberrant cytoplasmic localization of p120-catenin. Array-CGH analysis of IPH-926 revealed a profile of genomic imbalances that included many distinct alterations previously observed in primary ILBCs. Spectral karyotyping of IPH-926 showed a hyperdiploid chromosome complement and numerous clonal, structural aberrations. IPH-926 cells were anti-cancer drug-resistant, clonogenic in soft agar, and tumourigenic in SCID mice. In xenograft tumours, IPH-926 cells recapitulated the linear cord invasion pattern that defines ILBCs. In summary, IPH-926 significantly extends the biological spectrum of the established breast cancer cell lines and will facilitate functional analyses of genuine human ILBC cells in vitro and in vivo. Copyright (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

• Complete cytogenetic remission after decitabine treatment in a patient with secondary AML harbouring high p15 ( INK4b ) gene methylation and high global DNA methylation.

  Authors: Ulrich Lehmann, Christiane Dobbelstein, Martin Fenner, Daniel Römermann, Britta Hasemeier, Kathleen Metzig, Doris Steinemann, Guntram Büsche, Jürgen Krauter, Arnold Ganser, Hans Kreipe

  Annals of hematology. 09/2008;