Our Unit is specialized in the genomic analysis of malignant cells using molecular cytogenetics and other advanced genome technologies (CGH, microarrays, sequencing) to integrate conventional cytogenetics. Our aim is to search for new molecular events related to distinct clinical and/or pathological findings. Moreover we apply large molecular screenings by RT-PCR for emerging fusion genes, in order to be able to establish the incidence of a given rearrangement. All cases are carefully investigated at clinical, haematological and immunological level, according to the guidelines of WHO (World Health Organization) Classification for malignant hemopathies, with the aim of identifying distinct genetic-pathological entities. Our approach is based on restriction mapping of euchromatic and centric/pericentric regions involved in structural rearrangements by using FISH and molecular investigations such as RACE-PCR, and RT-PCR for candidate genes. Moreover we perform mutational analysis by both direct sequencing and DHPLC. We apply our mutational analysis in all cases with normal or failed karyotype, in cases with already known critical mutations, as well as checking for mutations of candidate genes regulating phenotypic features of leukemia subgroups. In order to identify early and aggressive genomic lesions in hematological malignancies we selected two different conditions. One of them is the B clonal lymphoproliferation arising in subjects with a hepatitis C virus infection which is emerging as an interesting model of B lymphomagenesis. Through the identification of clonal aberrations in sequential studies during the follow up of patients, we intend to trace critical steps of malignant transformation leading to a low grade lymphoma, such as marginal zone lymphoma in HCV-infected patients. As far as it concerns the significance of clonality in the context of a myelodyplastic bone marrow we will focus on two conditions: a long-lasting MDS, such as cytopenia with unilineage dysplasia, and the bone marrow insufficiency in Shwachman syndrome which may precede true MDS. We also use a FISH approach to develop new diagnostic tests for leukemic rearrangements by identifying and cloning new genes from rare chromosome rearrangements.