PhD student in Human Genetics
McGill University, MUHC – Montreal Children Hospital
Award-winning publication: Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
Published in: Nature, vol. 482, January 29 2012, p. 226-231.
"We sequenced the exomes of 48 paediatric gioblastoma multiforme (GBM) samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours, and associated with alternative lengthening of telomeres. Three recurrent mutations in H3F3A encoding histone variant H3.3 were observed in 31% of tumours. ATRX and DAXX required for H3.3 incorporation at pericentric heterochromatin and telomeres were identified in 31% of samples. H3F3A mutations are specific to GBM and highly prevalent in children and young adults."
This is a major genetic breakthrough that could change the way paediatric cancers are treated in the future. It helps explain the ineffectiveness of conventional treatments against cancer in children. Xiaoyang Liu showed that GBM in children is due to different molecular mechanisms than those in adults, and should not be treated in the same way. For the first time in humans the team has identified a mutation in one of the most important genes that regulates and protects our genetic information. This discovery is important in the developement of personalized medicine: treatment should be given to patients based on their genetic background. For patients with the mutations we identified, targeting this pathway should be considered, in order to get better treatment efficacy. The diagnosis of gliobastoma in a child or adolescent is currently a death sentence and about 200 children in Canada die every year of this cancer. By identifying the driver mutation in this disease, we opened the door and directed the way for more effective therapy, to save numerous lives.