Institute for Genetic and Biomedical Research (IRGB)

Research activities

Sardinian IRGB's scientific interests focus primarily on monogenetic and polygenetic studies and can be assembled in four wide ranges in research:

A. ProgeNIA project, a longitudinal study of a large cohort of Sardinian subjects
1) Study on quantitative traits of specific aspects of aging: mainly Cardiovascular component and Personality component
2) Study on about 300 quantitative traits and phenotypes of general biomedical interest

B. Complex diseases
1) Identification of the genes involved in pathogenesis of Type I Diabetes (TD1)
2) Identification of the genes involved in pathogenesis of Multiple Sclerosis (MS)
3) Next generation sequencing in Sardinian population for the identification of rare variants in MS and TD1
5) Research on genes involved in breast cancer.
6) Identification of the genes involved in the pathogenesis of the most common autoimmune diseases in Sardinia.
7) Functional studies on immunologic diseases.

C. Thalassemia, the most frequent monogenic disease in Sardinia
1) Genotype - phenotype relationship studies.
2) Identification of beta- thalassemia modifier genes.
3) Definition of thalassemia with intact globin gene.
4) Gene therapy.
5) Transcriptional regulation of globin genes.
6) Genes involved in Mesenchimal Staminal cells differentiation.

D. Monogenic diseases
1) Functional on the protein CRLF1 responsible for Crisponi's Syndrom
2) Functional studies on the protein AIRE responsible for autoimmune poliendocrinopathy type I (APECED).
3) Functional studies on FOXL2 gene, crucial for eye and ovary development.
4) Identification of the genes involved in overgrowth and dismorphic syndromes.

In the last few years, the research activity of the Milan section has developed along the genomics field with particular attention to the applications to human health. Therefore the Milan activity can be characterized as Translational Genomics.
The following themes are pursued:
1) Genetics of monogenic diseases, focussing on the pathologies of immune, cardiac and bone systems, as well as on some developmental syndromes such as Cornelia de Lange.
2) Genetics of polygenic diseases, with focus on cardiac pathologies.
3) Regenerative medicine. Animal models of bone and heart diseases are used to test novel approaches of cell therapy. In addition, the technologies needed to use induced pluripotent stem cells (iPSC) have been set up.
4) Oncology, genome stability and epigenetics that play a fundamental role both in cell differentiation and tumor pathogenesis.
5) New antibiotics. This research has recently been implemented, thanks to the collaboration with the private sector, in a joint project sponsored by the Regione Lombardia.
6) Role of sarcomeric proteins in cardiac and skeletal muscle function and disease such as dilated and hypertrophic cardiomyopathy, limb girdle muscular dystrophy, and nemaline myopathy.
7) Bioinformatics to integrate and support the study of genes and proteins involved in pathologic processes.

Precision medicine in Oncology: personalized approaches for diagnosis and treatment of cancer.

The Unit of Cancer Genetics at IRGB-CNR of Sassari is fully focused on precision medicine in oncological field, mostly based on translational research and, to a lesser extent, on basic research. In clinical practice, genomic and epigenomic profiling actually represents a crucial tool for the molecular classification of cancer patients in order to identify cases that might be responsive or resistant to the different innovative biological treatments (targeted therapy and immune-oncology). Usually, our group is committed to assess the genetic and molecular signatures at both DNA and RNA levels, generating data that firstly have an immediate clinical application and then contribute to the creation of large databases. These latter are useful for correlation between molecular and clinical or pathological features. Moreover, efforts are required to generate new bioinformatic tools for the most appropriate management of all produced information as well as to increase the use of multiparametric criteria toward the development of new algorithms for clinical classification during all phases of the disease progression.

In past years, the Unit of Cancer Genetics at CNR of Sassari has participated into the generation of the Cancer Registry of the Province of Sassari - which has now become the Cancer Registry of the Province of Sassari and Nuoro (thus, covering the Central-Northern Sardinia). It includes all cases diagnosed in the period between 1992 and 2016 (usually, registration of cases requires 4-5 years of work) and represents a crucial tool for evaluating not only the incidence and prevalence of cancers but also the rates of survival for patients in each specific geographical area. Such a Cancer Registry has been accredited by the Italian Cancer Registries Association (AIRTUM) and is officially recognized by the International Agency for Research on Cancer (IARC).

In addition to a tight collaboration with nearly all oncological institutions throughout the island - including an active participation into many multidisciplinary teams within the Sardinian health system (teams on breast cancer and melanoma were already officially registered), a fruitful interaction has been established with many health and research institutions across Italy (Institutes for Treatment and Research - so called IRCSS, scientific public and private Foundations, Health Units and Hospitals, Universities). Since, a large fraction of our research work is centered on studies on melanoma and non-melanoma skin cancers, the principal collaboration is within the Italian Melanoma Intergroup network.

Our Unit acts as a central laboratory for molecular diagnosis in oncology in Sardinia and, during past years, has analyzed thousands of biological samples from cancer patients within the Sardinian population, carrying out correlation studies on several malignancies aimed at identifying predictive and/or prognostic disease-associated markers for the improvement of the patients' management. In many series, we observed differences in the spectrum and distribution of genetic and molecular alterations within the Sardinian population. In recent years, we have also introduced analyzes on circulating tumor DNA (so called liquid biopsy) in order to both investigate tumor progression at any disease change (in a longitudinal way) and better monitor patients during treatments. Finally, our group is participating to genomic and molecular profiling in several clinical trials and studies (including a 7-year research project funded by AIRC); these activities are aimed at identifying predictive markers of response or resistance to innovative therapy protocols, especially for immunotherapy (where biomarkers are still missing).

The research activity is focused on the characterization of genetic and molecular factors involved in the susceptibility and pathogenesis of different types of solid neoplasms, more frequent - such as those in breast, ovary, prostate, lung, gastrointestinal sites, liver and biliary tract cancer, pancreas (the risk of developing these cancers in the course of life is high in Western countries) - and less frequent - such as melanoma (which has become a notable health and social problem due to the significant increase in incidence in recent years, especially among young people), GIST, mesothelioma, glioblastoma. This approach would allow a more accurate definition of the different molecular subtypes of cancer patients and a better characterization of the inter- and intra-tumor heterogeneity of each malignancy. A correct classification of cancer patients, on the basis of the personal "molecular pattern", is in fact considered indispensable for planning the patient's therapeutic strategy, in order to obtain an increasingly positive risk / benefit balance.

In particular, we proceed by pursuing the following objectives:

creation of specific databases containing all clinical, histological and biological information on cancer cases, with reconstruction of genealogies in order to identify and classify both familial and sporadic patients. The genetic and molecular data that are continuously produced by the genetic-molecular analyses on Sardinian cases are compared with those obtained from the analysis of neoplastic cases from other Italian regions;

identification and characterization of DNA sequence variants (polymorphisms and somatic/germline mutations) in candidate genes involved into the susceptibility and pathogenesis of the malignancies;

expression studies of candidate genes at somatic level, in vivo (on healthy and neoplastic tissues) and in vitro (on cultured cell lines), with qualitative (proteomic, immunohistochemical analysis) and quantitative (RT-PCR and real-time analysis) methods;

translational studies of association between genetic-molecular data and clinical-pathological parameters in neoplastic patients (histopathology, clinical stage and course, therapeutic response, survival), for the molecular classification of the different subgroups of neoplastic patients and definition of significant correlations with diagnosis, prognosis and therapeutic response (identification of susceptibility factors and prognostic and/or predictive markers of responsiveness/resistance to systemic medical treatments);

isolation and characterization of new genes involved in neoplastic development and progression. To date, the group has participated in the definition of the role in tumorigenesis of some candidate genes: BRAF, mutated in half of the cases of melanoma and become an important target for targeted biological therapies; h-PRUNE, involved in the formation of metastases in breast cancer; CASC2, a long non-coding RNA (lncRNA) associated with the pathogenesis of endometrial carcinoma and other cancers.

The research activity is conducted in close collaboration with the Department of Medical, Surgical and Experimental Sciences of the University of Sassari, and with numerous institutions at national level (CNR institutes, universities, local health units and university hospitals, scientific research & treatment institutes).
Ongoing projects and clinical trials

AIRC 5xmille: Epigenetic modeling/remodeling of cancer metastases and tumor immune contexture to improve efficacy of immunotherapy (

Molecular diagnosis in clinical oncology: convenzione con la AOU SS per la diagnosi molecolare oncologica (

Clinical Trial - BEYPRO2: An evaluation of the efficacy beyond progression of vemurafenib combined with cobimetinib associated with local treatment compared to second-line treatment in patients with BRAFV600 mutation-positive metastatic melanoma in focal progression with first-line combined vemurafenib and cobimetinib (

Clinical Trial - BIO-TAILOR (BIOliquid TAILOR study): Dabradenib and Trametinib in circulating free DNA BRAF mutated positive melanomas: a prospective phase II study (

Clinical trial - CaraMel: Clinical, dermoscopic, histological features and mutational status on primary melanoma multigene panels in patients with disease recurrence. (

Clinical trial - DISTINCTIVE Study: SeconD-line folfiri/aflIbercept in proSpecTIvely stratified, anti-EGFR resistaNt, metastatic coloreCTal cancer patIents with RAS Validated wild typE status (

Clinical Trial - SECOMBIT: Sequential Combo Immuno & Target therapy (SECOMBIT) study. A three arms prospective, randomized phase II study to evaluate the best sequential approach with combo immunotherapy (ipilimumab/ nivolumab) & combo target therapy (LGX818/MEK162) in patients with metastatic melanoma and BRAF mutation (

Clinical Trial - SUPERPEAK: Selection with a molecUlar PanEl foR Panitunumab Efficacy in K-ras and n-ras wild type metastatic colorectal cancer (