Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

Alexander Jethwa; Jennifer Hüllein; Tatjana Stolz; Carolin Blume; Leopold Sellner; Anna Jauch; Martin Sill; Arnon P Kater; G Doreen te Raa; Christian Geisler; Marinus van Oers; Sascha Dietrich; Peter Dreger; Anthony D Ho; Anna Paruzynski; Manfred Schmidt; Christof von Kalle; Hanno Glimm; Thorsten Zenz

doi:10.1111/bjh.12539

Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

Alexander Jethwa, Jennifer Hüllein, Tatjana Stolz, Carolin Blume, Leopold Sellner, Anna Jauch, Martin Sill, Arnon P Kater, G Doreen te Raa, Christian Geisler, Marinus van Oers, Sascha Dietrich, Peter Dreger, Anthony D Ho, Anna Paruzynski, Manfred Schmidt, Christof von Kalle, Hanno Glimm, Thorsten Zenz

43 Citations (Scopus)

Abstract

Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently mutated (16.3%, 16.9%, 10.7%). We found evidence for subclonal mutations in 67.5% of CLL cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in CLL. Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in CLL.

Original language	English
Journal	British Journal of Haematology
Volume	163
Issue number	4
Pages (from-to)	496-500
Number of pages	5
ISSN	0007-1048
DOIs	https://doi.org/10.1111/bjh.12539
Publication status	Published - Nov 2013

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Jethwa, A., Hüllein, J., Stolz, T., Blume, C., Sellner, L., Jauch, A., Sill, M., Kater, A. P., te Raa, G. D., Geisler, C., van Oers, M., Dietrich, S., Dreger, P., Ho, A. D., Paruzynski, A., Schmidt, M., von Kalle, C., Glimm, H., & Zenz, T. (2013). Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia. British Journal of Haematology, 163(4), 496-500. https://doi.org/10.1111/bjh.12539

Jethwa, A, Hüllein, J, Stolz, T, Blume, C, Sellner, L, Jauch, A, Sill, M, Kater, AP, te Raa, GD, Geisler, C, van Oers, M, Dietrich, S, Dreger, P, Ho, AD, Paruzynski, A, Schmidt, M, von Kalle, C, Glimm, H & Zenz, T 2013, 'Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia', British Journal of Haematology, vol. 163, no. 4, pp. 496-500. https://doi.org/10.1111/bjh.12539

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title = "Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia",

abstract = "Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently mutated (16.3\%, 16.9\%, 10.7\%). We found evidence for subclonal mutations in 67.5\% of CLL cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in CLL. Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in CLL.",

author = "Alexander Jethwa and Jennifer H{\"u}llein and Tatjana Stolz and Carolin Blume and Leopold Sellner and Anna Jauch and Martin Sill and Kater, \{Arnon P\} and \{te Raa\}, \{G Doreen\} and Christian Geisler and \{van Oers\}, Marinus and Sascha Dietrich and Peter Dreger and Ho, \{Anthony D\} and Anna Paruzynski and Manfred Schmidt and \{von Kalle\}, Christof and Hanno Glimm and Thorsten Zenz",

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year = "2013",

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T1 - Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

AU - Jethwa, Alexander

AU - Hüllein, Jennifer

AU - Stolz, Tatjana

AU - Blume, Carolin

AU - Sellner, Leopold

AU - Jauch, Anna

AU - Sill, Martin

AU - Kater, Arnon P

AU - te Raa, G Doreen

AU - Geisler, Christian

AU - van Oers, Marinus

AU - Dietrich, Sascha

AU - Dreger, Peter

AU - Ho, Anthony D

AU - Paruzynski, Anna

AU - Schmidt, Manfred

AU - von Kalle, Christof

AU - Glimm, Hanno

AU - Zenz, Thorsten

PY - 2013/11

Y1 - 2013/11

N2 - Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently mutated (16.3%, 16.9%, 10.7%). We found evidence for subclonal mutations in 67.5% of CLL cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in CLL. Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in CLL.

AB - Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently mutated (16.3%, 16.9%, 10.7%). We found evidence for subclonal mutations in 67.5% of CLL cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in CLL. Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in CLL.

UR - https://www.scopus.com/pages/publications/84886392472

U2 - 10.1111/bjh.12539

DO - 10.1111/bjh.12539

M3 - Journal article

C2 - 24032483

SN - 0007-1048

VL - 163

SP - 496

EP - 500

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 4

ER -

Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

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