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Researchers discover 40 genes involved in early development of myeloma

Researchers have increased the understanding of the complex genetics behind an incurable blood cancer.

The Institute of Cancer Research, London, has conducted a study which has revealed 40 genes involved in the development of myeloma, enhancing the knowledge about the complex genetics associated with this condition.

The study findings will help encourage the development of more personalised treatments for myeloma, which is the second most common blood cancer in the UK. Approximately 5500 people in the UK are diagnosed with this type of cancer every year.

The team, based at The Institute of Cancer Research, London, and largely funded by the charity Myeloma UK, uncovered new areas of coding, and non-coding DNA, that drive the early progression of myeloma.

The research was published in the journal Leukemia, and was supported by Bloodwise and Cancer Research UK.

The researchers, led by Professor Richard Houlston and Dr Martin Kaiser at The Institute of Cancer Research (ICR), analysed the whole genome sequencing (WGS) data from 804 people with myeloma alongside the whole exome sequencing (WES) data of 765 myeloma patients.

They found that 16 genes were disrupted in coding regions of DNA, and 15 in non-coding areas.

Tumour suppressors PAX5 and HOXB3 were found to be downregulated by non-coding mutations, consistent with their decreased expression contributing to the development and progression of myeloma, also seen in other B cell cancers.

The ICR researchers have now added TWEAK, TRAF2 and PRKD2 to the list of genes in myeloma that are disrupted by coding mutations, COBLL1 as dysregulated by mutations in non-coding DNA, and MAP3K14 as upregulated by DNA reorganisation.

Commenting on the research, Professor Richard Houlston, professor of molecular and population genetics at The Institute of Cancer Research, London, said: “We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer. Exhaustive genetic research like this is helping us to make that possible.

Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Dr Simon Ridley, director of research at Myeloma UK, said: “This new research is a valuable step forward in our understanding of the complex genetic changes which drive myeloma.

“More research investment is needed to understand fully the genetic and molecular processes behind myeloma and related diseases, and to translate this knowledge towards patient benefit.”

Myeloma UK said increasing its knowledge of the complex pathways driving the development and progression of myeloma, “is going to be key to identifying new myeloma therapies, and to enable the tailoring of patient treatments”.

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