Real‐time PCR‐based analysis of BRAF V600E mutation in low and intermediate grade lymphomas confirms frequent occurrence in hairy cell leukaemia

Hairy cell leukaemia (HCL) is a rare type of B‐cell non‐Hodgkin lymphoma (B‐NHL), which is not known to be associated with any characteristic recurrent karyotypic abnormality. A recent study that used massively parallel whole exome sequencing identified an activating V600E mutation in BRAF, which appeared specific for HCL. Here, we confirm the specificity of BRAF V600E for HCL among low and intermediate grade B‐NHL and describe a real‐time polymerase chain reaction method for detecting this mutation in cases with low tumour burden. The V600E mutation does not appear to be associated with microsatellite instability, unlike the case in colorectal cancer. Thus, in conjunction with prior data, our results suggest incorporation of BRAF V600E mutation analysis in the diagnostic workup of HCL cases. Additionally, targeting the Ras‐Raf‐Mek‐Erk‐Map kinase pathway should be investigated as a potential therapeutic strategy for patients with this disease. Copyright © 2011 John Wiley & Sons, Ltd.

[1]  P. Gaulard,et al.  The mechanisms underlying MMR deficiency in immunodeficiency‐related non‐Hodgkin lymphomas are different from those in other sporadic microsatellite instable neoplasms , 2009, International journal of cancer.

[2]  J. Cawley,et al.  The biology of hairy-cell leukaemia , 2010, Current opinion in hematology.

[3]  M. Pombo-de-Oliveira,et al.  DNA extraction from fixed cytogenetic cell suspensions. , 2007, Genetics and molecular research : GMR.

[4]  C. Worman,et al.  HAIRY‐CELL LEUKAEMIA , 1985, British journal of haematology.

[5]  Trevor J Pugh,et al.  Initial genome sequencing and analysis of multiple myeloma , 2011, Nature.

[6]  G. Follows,et al.  High resolution melting analysis for detection of BRAF exon 15 mutations in hairy cell leukaemia and other lymphoid malignancies , 2011, British journal of haematology.

[7]  M. Piris,et al.  Evolving concepts in the pathogenesis of hairy-cell leukaemia , 2006, Nature Reviews Cancer.

[8]  J. Cawley The Biology of Hairy Cell Leukemia , 2009, Leukemia & lymphoma.

[9]  S. Pileri,et al.  BRAF mutations in hairy-cell leukemia. , 2011, The New England journal of medicine.

[10]  S. Schwartz,et al.  Activated BRAF targets proximal colon tumors with mismatch repair deficiency and MLH1 inactivation , 2004, Genes, chromosomes & cancer.

[11]  S. Benlloch,et al.  Detection of BRAF V600E mutation in colorectal cancer: comparison of automatic sequencing and real-time chemistry methodology. , 2006, The Journal of molecular diagnostics : JMD.

[12]  S H Lee,et al.  BRAF mutations in non-Hodgkin's lymphoma , 2003, British Journal of Cancer.

[13]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.