Researchers discover new, recurrent genetic mutation in lymphoma

Vancouver, BC – Researchers based at the BC Cancer Agency’s Centre for Lymphoid Cancer in Vancouver and funded by the Terry Fox Foundation have discovered a new, recurrent genetic mutation in two kinds of lymphoma — Hodgkin lymphoma and primary mediastinal B-cell lymphoma (PMBCL).

Their findings, published February 16 in Nature Genetics, provide scientific proof that the altered gene PTPN1 plays a role in human cancer and point to the possibility of a new way to personalize treatment for lymphoma patients. PMBCL is a distinct subtype of aggressive B-cell lymphoma which affects predominantly young females but may also occur in children and adolescents.

Study lead Dr. Christian Steidl, department of experimental therapeutics at the BC Cancer Research Centre and an assistant professor of pathology at the University of British Columbia, said the discovery is a world first.

“Our work identifies, for the first time, the entirety of genetic mutations in primary mediastinal B-cell lymphoma and first-of-its kind-mutations in the PTPN1 gene,” said Dr Steidl.

He added that the study shows how cancer cells profit from these genetic mutations to the detriment of affected patients through activation of cellular signaling that ultimately leads to tumour growth.

The discovery is promising for lymphoma patients who carry these mutations because it provides potential new targets for treating the disease with new therapeutics, including for those who do not respond to standard treatment, he said.

For the study, investigators used high throughput sequencing to analyze the whole-genome and whole transcriptome of 10 index samples, which was followed by targeted sequencing of about 100 human samples and lab-developed cell-lines which revealed “highly recurrent and novel gene mutations in the PTPN1 gene.” The Vancouver Centre has one of the largest collections of these samples in the world.

Dr. Steidl is a principal investigator on the Terry Fox New Frontiers Program Project Grant in Molecular Correlates of Treatment Failure in Lymphoid Cancers (2013-2106). The programs are managed by TFRI.