Children with rare bone tumour have lost DNA

How can we explain the sudden development of an osteosarcoma in healthy children and young adults? These fast-growing and aggressive bone tumours are rare, but when they do occur they are often fatal. PhD candidate Alexander Mohseny hopes to find new possibilities for treatment. PhD defence  27 June.

First the origin of the tumour then the biology

Transformed stem cells can still differentiate into other cell types.

Mohseny: ‘Earlier studies have shown that you cannot arrive at new treatment methods for the osteosarcoma if you don't understand the origin and the biology of the tumour. First, you have to answer questions about which cells we have to attack, what are the processes that have been disturbed and whether we can repair these processes.'  

Early precursors

One of the first and most important findings was that the osteosarcoma probably didn't develop from normal bone cells (osteoblasts) but from their early precursors (mesenchymal stem cells). These cells also appear to transform into malignant cells because they suddenly lose an important piece of DNA (Cdkn2A). Loss of the DNA deactivates two crucial processes in the cell: the control of cell growth and cell death. These processes normally stop malignant deterioration of cell growth.

Diagram of the osteosarcoma stem cell model.

Multi-pronged attack

This was not the only discovery. Mohseny: ‘When the cells have been transformed, not only are they able to move and spread, they can also undermine the body's immune system.' But this doesn't answer the question of why the process starts. It's difficult to explain,' according to Mohseny. ‘There may be several different factors at play, and internal and external stimuli damage the same cell at the same time.  This could explain the sudden development of the tumour and why it is so rare.'

A zebrafish embryo is a 'miniature laboratory'

The zebrafish is a popular animal model.

This research makes use of a mesenchymal stem cell model of a mouse and of tumours and cell lines of osteosarcoma patients.  'We also used zebrafish embroys as miniature laboratories', Mohseny explains, 'to examine the characteristics of transformed cells as a way of rapidly and efficiently studying transformed cells.'

Mohseny intends to carry on with his research: ‘There are still so many unanswered questions.’

PhD defence

Alexander Mohseny
Osteosarcoma Models: Understanding Complex Disease
27 June, 10.00 hrs
Academy Building, Rapenburg 73, Leiden
Faculty of Medicine
Supervisor: Professor Pancras Hogendoorn

(24 June 2012)

Links

• Bone and soft tissue tumour pathology research group
  
  

• Health across the human life cycle is one of the six themes for research at Leiden University

Studying in Leiden

Bachelor's in Medicine and master's in Medical Sciences