Multiple myeloma (MM) is a cancer of plasma cells, which are mature white blood cells within the bone marrow. The disease causes bone pain and weakening which often leads to fractures. It typically affects people over the age of 60, with about 1700 new diagnoses each year in Australia. It is incurable and carries a life expectancy of 2-7 years depending on the aggressiveness of the tumour cells. Although the actual cause of MM is unknown, it is often preceded by less severe forms of the disease called monoclonal gammopathy of undetermined significance (MGUS), and smouldering multiple myeloma (SMM). However, not everyone with these early stages will develop MM, and it is not clear what drives progression of the disease. 

The aim of this study is to improve the laboratory methods used to clinically evaluate patients with MGUS, SMM and MM in order to better evaluate the aggressiveness of the tumour cells and look for clues as to why some patients with MGUS or SMM are more likely to progress to Myeloma.

We will do this by employing technology that is easily translatable into diagnostic platform. Our initial work indicates that a technology known as HD SNP (high density single nucleotide polymorphism) microarray along with molecular based fusion gene-sequencing panels by next generation sequencing (NGS) can potentially   identify changes across the entire genome (i.e. entire genetic material contained in  the plasma cell) for patients with MGUS, SMM and MM. Routine  clinical testing for genetic changes in Myeloma is currently done by  techniques known as  karyotype and fluorescent in situ hybridization (FISH). This technology has been in use for over 30 years and  is successful only in 20-30 % of plasma cell disorders and has a resolution. The FISH technology has been in use for about 15-20 years and uses probes that can detect focal changes and genetic translocations very accurately but large cumbersome panels are needed to detect the range of changes observed in Myeloma.
We propose to validate SNP microarray and molecular based fusion gene-sequencing so it can be implemented in routine practise via NSW health Pathology, the public pathology service of the NSW Health. The patients will be chosen from a bank of over 200 samples already available within the Hunter Haematology group’s myeloma cohort. 

We also aim to explore the genome wide changes in plasma cells across the spectrum of MGUS, SMM and MM to understand the genome wide changes that occur across this spectrum.  We will compare the CNV (copy number variation), cnLOH (copy neutral loss of heterozygosity) and methylation in this cohort. This will provide an important insight into the understanding the role of genome wide changes in the progression from MGUS to Myeloma. This may provide a basis for interventions, such as immunodulation or immunotherapy, with potential to prevent progression of the precursor lesions such as  MGUS or SMM into MM.


Dr Anoop Enjeti, Ms Nadine Berry, Dr Wojt Janowski, L/Prof Rodney Scott, Prof Philip Rowlings

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