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.
authors.affiliation: Department of Translational Oncology, National Centre for Tumour Diseases (NCT) and German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jethwa
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hüllein
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stolz
authors.forename: Carolin
authors.initials: C
authors.lastname: Blume
authors.forename: Leopold
authors.initials: L
authors.lastname: Sellner
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Martin
authors.initials: M
authors.lastname: Sill
authors.forename: Arnon P
authors.initials: AP
authors.lastname: Kater
authors.forename: G Doreen
authors.initials: GD
authors.lastname: te Raa
authors.forename: Christian
authors.initials: C
authors.lastname: Geisler
authors.forename: Marinus
authors.initials: M
authors.lastname: van Oers
authors.forename: Sascha
authors.initials: S
authors.lastname: Dietrich
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Anna
authors.initials: A
authors.lastname: Paruzynski
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Hanno
authors.initials: H
authors.lastname: Glimm
authors.forename: Thorsten
authors.initials: T
authors.lastname: Zenz
mesh_terms: D015331:Cohort Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods*; D015398:Signal Transduction
keywords: NOTCH1; SF3B1; TP53; chronic lymphocytic leukaemia; convergent mutation