Molecular and Gene Expression Studies of Lymphoma

The Genomics Research Centre based at QUT is currently undertaking biomedical research on non-Hodgkin’s Lymphoma (NHL) in a project originally termed the Griffith Lymphoma Project (GLP) which commenced in 2002 to investigate the molecular pathogenesis of lymphomas. Cancer detection and treatment remains a significant problem in society. Approaches to detect and treat cancers have improved in recent years, but we are still limited to largely generic approaches for individual risk stratification and treatment. Our research has been involved in investigating both detection and treatment of NHL using genetic samples from patients and their cancers. Specifically, we are studying the influence of genetic factors on disease susceptibility by examining gene variation in lymphoma patients and healthy individuals. This allows us to see whether these variations are involved in the genesis of lymphoma or in the development of specific characteristics of the disease. Our research aims to provide information that is useful in predicting who is at risk of developing lymphoma and also how to develop targeted new treatments.

Our research has aimed to investigate genetic variation and identify genes involved in the development of NHL through the use of both tumour tissue samples and genomic DNA from NHL and control patients. We have used individual gene analysis and also whole genome approaches to investigate genetic variation and gene expression differences in samples from NHL patients versus normal controls. These approaches have allowed us to identify aberrations within individual genes, and also in gene pathways, with results implicating specific genes, including PTPRJ and FOXP1 in cancer development and progression. We have identified regions in the genome containing potential tumour suppressor genes (that drive cancer when inactivated) that may result in the pathogenesis of FL and DLBCL, including TP53BP1, B2M and PTPRJ. We also showed a genetic association of NHL risk with variation in the PTPRJ gene using cases and controls. We have identified two novel mutations in DLBCL tumour DNA in the FOXP1 gene and also determined a significant association of 6 genes with FOXP1 expression in DLBCL tumour tissues indicating that these FOXP1 target genes are associated with aggressive disease. Recently, we combined high-resolution whole genome genetic variation analysis (SNParrays), gene set enrichment analysis and comparison gene expression analysis of primary tumour samples, to identify conserved genetic alterations between the common NHL sub-types. This approach allowed us to identify aberrations within gene regions and gene pathways that are shared across the different NHL sub-types identifying common genetic factors in NHL. From this analysis, we identified a number of genes and regions implicated in NHL development providing information to aid in future risk profiling and for new drug targets.

These projects have resulted in a number of published papers (13 to date – which we are happy to send on to interested readers) and many presentations (24 to date) at conferences, as well as research training development for several young, enthusiastic and promising medical research PhD students.

 

Help Needed

These studies have been undertaken with the help of NHL patients and also normal control individuals who have donated samples for our research. To continue these studies and to have greater power to detect and investigate genes implicated in NHL, we need access to more samples for analysis. In particular for the NHL susceptibility studies we have DNA from 318 NHL patients and 158 healthy controls. To gain a more thorough understanding and statistically stronger results, the GRC is calling on the public to build-up their numbers of volunteer samples by donating blood.

The GRC is now aiming to collect around 300 NHL cases and also 300 control samples – that is, people who have not been diagnosed with cancer. The blood donation takes only 5 minutes and will aid in our research for around the next 5-10 years. Where possible, NHL participants may also contribute tissue taken from their tumours following surgery, so that genomic data from tumours and patients can be compared for additional analysis types.

If you have or have ever had a confirmed diagnosis of NHL and you would like to participate in our research- please volunteer to help by making a single blood donation and providing accompanying questionnaire information- and considering being involved with a friend as it would be very helpful for us to have normal (control) individuals to aid in this research also through a single blood sample and questionnaire.

If you or someone you know are interested in supporting this research, please contact us on the details below.

Genomics Research Centre, IHBI, QUT

Lymphoma project contact person – Gabrielle Bradshaw 0467 617 457 or gabrielle.bradshaw@hdr.qut.edu.au