Research project

Investigating the loss of Profilin 1 as the driver event for genomic instability in osteosarcoma (DSB.AD001.182)

Thematic area

Biomedical sciences

Project area

Oncologia e Immunologia (DSB.AD001)

Structure responsible for the research project

Institute of genetics and biophysics "Adriano Buzzati Traverso" (IGB)

Project manager

Phone number: +390816132255


Genomic instability represents a hallmark of most cancers, including osteosarcoma, breast, pancreas, ovarian and lung cancers.
We identified PFN1 as causative gene in osteosarcoma associated with Paget's disease of bone (OS/PDB), and disclosed its
genomic loss also in primary osteosarcomas. PFN1 encodes the Profilin 1, involved in cytoskeleton organization and cell cycle
regulation. Downregulation of PFN1 has been observed also in other cancers (breast, pancreas, bladder, liver). Pfn1-KO MC3T3
and mesenchymal cells isolated from our Pfn1-KI mouse model display features of malignant transformation: increased
proliferation rate and nuclear abnormalities, namely polyploidy, chromatin bridges and micronuclei containing damaged DNA.
These characteristics are indicative of cell division defects that result in chromosomal instability. In fact, whole genome
sequencing (WGS) on four OS/PDB samples revealed high burden of chromosomal rearrangements and copy number changes.

Start date of activity



Profilin 1, Osteosarcoma, Genomic instability

Last update: 01/12/2023