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Exome sequencing in classic hairy cell leukaemia reveals widespread variation in acquired somatic mutations between individual tumours apart from the signature BRAF V(600)E lesion

Exome sequencing in classic hairy cell leukaemia reveals widespread variation in acquired somatic mutations between individual tumours apart from the signature BRAF V(600)E lesion
Exome sequencing in classic hairy cell leukaemia reveals widespread variation in acquired somatic mutations between individual tumours apart from the signature BRAF V(600)E lesion
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 V(600)E 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 V(600)E, 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 V(600)E to drive pathogenesis of malignant HCLc disease.
1932-6203
1-14
Weston-Bell, Nicola J.
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Tapper, Will
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Gibson, Jane
855033a6-38f3-4853-8f60-d7d4561226ae
Bryant, Dean
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Moreno, Yurany
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John, Melford
690302e8-0e9a-4f67-ba71-341dbcae5ef0
Ennis, Sarah
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Kluin-Nelemans, Hanneke C.
243d2cac-e859-4b13-94cb-382f0f3e19a7
Collins, Andrew R.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Sahota, Surinder S.
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Weston-Bell, Nicola J.
c99c8c28-519f-4c3e-bd8c-679995a0472e
Tapper, Will
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Gibson, Jane
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Bryant, Dean
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Moreno, Yurany
82940fd5-60d6-43ce-a7a8-b39f41e2dccd
John, Melford
690302e8-0e9a-4f67-ba71-341dbcae5ef0
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Kluin-Nelemans, Hanneke C.
243d2cac-e859-4b13-94cb-382f0f3e19a7
Collins, Andrew R.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Sahota, Surinder S.
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Weston-Bell, Nicola J., Tapper, Will, Gibson, Jane, Bryant, Dean, Moreno, Yurany, John, Melford, Ennis, Sarah, Kluin-Nelemans, Hanneke C., Collins, Andrew R. and Sahota, Surinder S. (2016) Exome sequencing in classic hairy cell leukaemia reveals widespread variation in acquired somatic mutations between individual tumours apart from the signature BRAF V(600)E lesion. PLoS ONE, 11 (2), 1-14, [e0149162]. (doi:10.1371/journal.pone.0149162). (PMID:26871591)

Record type: Article

Abstract

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 V(600)E 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 V(600)E, 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 V(600)E to drive pathogenesis of malignant HCLc disease.

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Accepted/In Press date: 28 January 2016
e-pub ahead of print date: 12 February 2016
Published date: 12 February 2016
Organisations: Faculty of Medicine

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Local EPrints ID: 388476
URI: http://eprints.soton.ac.uk/id/eprint/388476
ISSN: 1932-6203
PURE UUID: 0835e6c7-9f10-4103-9f7b-738c3b956063
ORCID for Nicola J. Weston-Bell: ORCID iD orcid.org/0000-0003-0075-7276
ORCID for Will Tapper: ORCID iD orcid.org/0000-0002-5896-1889
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Andrew R. Collins: ORCID iD orcid.org/0000-0001-7108-0771

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Date deposited: 26 Feb 2016 08:59
Last modified: 18 Feb 2021 17:08

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Contributors

Author: Nicola J. Weston-Bell ORCID iD
Author: Will Tapper ORCID iD
Author: Jane Gibson ORCID iD
Author: Dean Bryant
Author: Yurany Moreno
Author: Melford John
Author: Sarah Ennis ORCID iD
Author: Hanneke C. Kluin-Nelemans
Author: Surinder S. Sahota

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