Tumor epigenetics

The post genomic era has shown that transcription factors are not unique key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, post-translational modifications of histone proteins, remodeling of nucleosomes and expression of small regulatory RNAs contribute to regulate gene expression, to define cell and tissue specific gene expression patterns and to assure the inheritance of information based on gene expression levels. Our current research investigates the role of genetic and epigenetic alterations in the development of sporadic cancers, with a focus on acute myeloid leukemia. We use genome wide approaches as Restriction Landmark Genome Scanning (RLGS), BAC microarrays (methylation-array) and conventional array-CGH to identify specific patterns of epigenetic and genetic aberrations in tumor samples. The statistical analyses of the results provide useful information to increase our knowledge of the epigenetic and genetic aberrations of different histological subtypes of the same kind of tumor, to predict their chemo-sensitivity and possibly the clinical outcome.

Unit members

Selected publications

Zardo G, Cimino G, Nervi C. Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/progenitor cells: therapeutic potential of cell reprogramming.Leukemia. 2008 22:1503-18.

Fazi F, Zardo G, Gelmetti V, Travaglini L, Ciolfi A, Di Croce L, Rosa A, Bozzoni I, Grignani F, Lo-Coco F, Pelicci PG, Nervi C. Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia. Blood. 2007 14; 4432-40

Guccione E, Martinato F, Finocchiaro G, Luzi L, Tizzoni L, Dall' Olio V, Zardo G, Nervi C, Bernard L, Amati B. (2006) Myc-binding-site recognition in the human genome is determined by chromatin context. Nat Cell Biol. 8: 764-70.

Zardo, G., Reale, A., Passananti, C., Pradhan S., Buontempo, S., De Matteis, G., Adams, R.L.P. and Caiafa P. (2002): Inhibition of poly(ADP-ribosyl)ation induces DNA hypermethylation: a possible molecular mechanism. The FASEB Journal 16, 1319-1321.

Zardo, G., Tiirikainen, M.I., Hong, C., Misra, A., Feuerstein, B.G., Volik, S., Collins, C.C., Lamborn K.R., Bollen, A., Pinkel, D., Albertson D.G. and Costello J.F. (2002): Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumours. Nature Genet. 32, 453-458.