PHG Foundation | Single common gene variant found in hairy cell leukemia

PHG Foundation | Single common gene variant found in hairy cell leukemia: "Single common gene variant found in hairy cell leukemia
Analysis of a study published in a science journal | By Dr Sowmiya Moorthie | Published 16 June 2011
Study: BRAF Mutations in Hairy-Cell Leukemia
By: Tiacci E. et al. (36 authors total)
In: New England Journal of Medicine
Link: http://dx.doi.org/10.1056/NEJMoa1014209

What this study set out to do:

To identify somatic mutations within protein coding genes that are present in most people with hairy cell leukemia (HCL) in order to understand the biology of the disease.
How they went about it:

DNA was extracted from normal and tumour cells of a patient with HCL and the exome sequenced using massively parallel sequencing. Comparison with the human genome reference sequence and bioinformatic analysis were used to identify somatic mutations present only in the tumour cells. PCR and Sanger sequencing verified these candidate mutations. Individuals with HCL as well as other blood cancers such as B-cell lymphomas or leukemias were screened for the presence of one particular variant – BRAF V600E. The effect of BRAF inhibitors on downstream cell signalling was also investigated.
Outcome:

Five variants present in the tumour DNA were identified and verified by Sanger sequencing. The BRAF V600E mutation was present in all individuals with HCL but not other blood cancers. A mutation in the BRAF gene results in constitutive activation of downstream signalling proteins MEK and ERK, which was reduced by a specific inhibitor of BRAF.
Conclusion:

The authors conclude that analysis of BRAF mutations maybe used to diagnose HCL by distinguishing it from other blood cancers with the same symptoms, and these mutations could be a target for therapies. This would be especially useful for those individuals who do not respond to current therapies.
Our view:

The findings reported in this paper have implications for the diagnosis and treatment of HCL as well as providing an insight into the disease. However, the authors need to validate their findings in a larger population. This study also demonstrates how new sequencing technologies can be used in improving our understanding of cancer.

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