Translation gene expression profiling of Fibrous Dysplasia into clinical setting: NanoString technology approach for Formalin-Fixed Paraffin-Embedded biopsies.

Anno
2017
Proponente Domenico Raimondo - Professore Associato
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Categoria
Edoardo Milanetti Dottorando/Assegnista/Specializzando componente il gruppo di ricerca
Abstract

Fibrous Dysplasia (FD) is a genetic skeletal disorder characterized by thinning of cortical bone and replacement of the bone marrow with fibro-osseous tissue. The underlying defect in fibrous dysplasia is a mutation of the GNAS gene, which leads to constitutive activation of gene products that interfere with the maturation of osteoprogenitor cells and lead to deposition of abnormal bone. Two studies conducted so far have been performed on the mRNA expression analysis of human fibrous dysplastic bone tissues employing microarray approach to explore the key molecule events in FD development. The present proposal aims at generating mRNA expression profiling of FD clinical samples stored in formalin-fixed paraffin embedded (FFPE) blocks using NanoString platform technology. This platform hybridizes fluorescent barcodes directly to specific nucleic acid sequences, allowing for the nonamplified measurement of up to 800 targets within one sample, working well with FFPE samples. The specific aims of this proposal include: 1) the identification of genes that are differently expressed in fibrous versus non-fibrous human bone in FFPE paraffin blocks; 2) the description of relationships between these genes using multivariate data analysis to search for gene clusters which separate and can characterize the healthy state from the pathologic one; 3) the assesment that NanoString technology has the potential to penetrate into clinical diagnostic practice proving to be robust and reliable for quantification of RNA species extracted from Fibrous Dysplasia clinical samples stored in FFPE blocks. This approach will eventually lead to develop relevant molecular biomarkers to monitor the efficacy of treatments and/or disease progression. Finally the translation of state-of-the-art technology like NanoString approach into quantifiable patient benefits such as the development of effective biomarkers could be extremely attractive also into clinical settings other than FD.

ERC
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