B-cell malignancies: capture-sequencing strategies for identification of gene rearrangements and translocations into immunoglobulin gene loci

Abstract

Eileen M Boyle,1,2 Brian A Walker,1 Christopher P Wardell,1 Xavier Leleu,2 Faith E Davies,1 Gareth J Morgan1 1Centre for Myeloma Research, Institute of Cancer Research, Sutton, Surrey, UK; 2Service des Maladies du Sang, Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille, France Abstract: Aberrant chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus and clonal rearrangements of the variable (V), diversity (D), joining (J) segments (V[D]J) of the immunoglobulin gene are implicated in the initiation of mature B-cell malignancies, including myeloma. Analysis of these events provides information useful for diagnosis and prediction of prognosis, and also provides a useful monitoring strategy for response to treatment in patients with these diseases. Current methods for identification of these events are not generally applicable and give a biased picture of the prognostic significance and clinical relevance of these events. Novel methodologies based on next-generation sequencing are a new and more efficient genetic tool that can be used to screen and characterize these changes at the nucleotide level, offering a deeper and better understanding of the genetic basis of these complex diseases. In this work, we provide a review of the molecular basis of B-cell neoplasms, the methods used to detect them, and how they translate into the clinic. Keywords: B-cell malignancies, minimal residual disease, molecular, IGH locus, next-generation sequencing