Exome Sequencing in Classic Hairy Cell Leukaemia Reveals Widespread Variation in Acquired Somatic Mutations between Individual Tumours Apart from the Signature BRAF V600E LesionReportar como inadecuado




Exome Sequencing in Classic Hairy Cell Leukaemia Reveals Widespread Variation in Acquired Somatic Mutations between Individual Tumours Apart from the Signature BRAF V600E Lesion - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

In classic Hairy cell leukaemia HCLc, a single case has thus far been interrogated by whole exome sequencing WES in a treatment naive patient, in which BRAF V600E was identified as an acquired somatic mutation and confirmed as occurring near-universally in this form of disease by conventional PCR-based cohort screens. It left open however the question whether other genome-wide mutations may also commonly occur at high frequency in presentation HCLc disease. To address this, we have carried out WES of 5 such typical HCLc cases, using highly purified splenic tumour cells paired with autologous T cells for germline. Apart from BRAF V600E, no other recurrent somatic mutation was identified in these HCLc exomes, thereby excluding additional acquired mutations as also prevalent at a near-universal frequency in this form of the disease. These data then place mutant BRAF at the centre of the neoplastic drive in HCLc. A comparison of our exome data with emerging genetic findings in HCL indicates that additional somatic mutations may however occur recurrently in smaller subsets of disease. As mutant BRAF alone is insufficient to drive malignant transformation in other histological cancers, it suggests that individual tumours utilise largely differing patterns of genetic somatic mutations to coalesce with BRAF V600E to drive pathogenesis of malignant HCLc disease.



Autor: Nicola J. Weston-Bell , Will Tapper , Jane Gibson, Dean Bryant, Yurany Moreno, Melford John, Sarah Ennis, Hanneke C. Kluin-Nelema

Fuente: http://plos.srce.hr/



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