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Review
. 2018 Apr 20;19(4):1251.
doi: 10.3390/ijms19041251.

What Does This Mutation Mean? The Tools and Pitfalls of Variant Interpretation in Lymphoid Malignancies

Yann Guillermin  1 , Jonathan Lopez  2   3   4 , Kaddour Chabane  5 , Sandrine Hayette  6   7 , Claire Bardel  8   9 , Gilles Salles  10   11   12 , Pierre Sujobert  13   14   15 , Sarah Huet  16   17   18
Affiliations
Review

What Does This Mutation Mean? The Tools and Pitfalls of Variant Interpretation in Lymphoid Malignancies

Yann Guillermin et al. Int J Mol Sci. .

Abstract

High throughput sequencing (HTS) is increasingly important in determining cancer diagnoses, with subsequent prognostic and therapeutic implications. The biology of cancer is becoming increasingly deciphered and it is clear that therapy needs to be individually tailored. Whilst translational research plays an important role in lymphoid malignancies, few guidelines exist to guide biologists and routine laboratories through this constantly evolving field. In this article, we review the challenges of interpreting HTS in lymphoid malignancies and provide a toolkit to interpret single nucleotide variants obtained from HTS. We define the pre-analytical issues such as sequencing DNA obtained from formalin-fixed and paraffin-embedded tissue (FFPE), the acquisition of germline DNA, or the bioinformatic pitfalls, the analytical issues encountered and how to manage them. We describe the main constitutional and cancer databases, their characteristics and limitations, with an emphasis on variant interpretation in lymphoid malignancies. Finally, we discuss the challenges of predictions that one can make using in silico or in vitro modelling, pharmacogenomic screening, and the limits of those prediction tools. This description of the current status in genomic interpretation highlights the need for new large databases and international collaboration in the lymphoma field.

Keywords: lymphoid malignancies; next-generation sequencing; variant interpretation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mutation frequencies in different lymphoma entities. Abbreviations: CLL: chronic lymphocytic leukemia; SLL: small lymphocytic lymphoma; MCL: mantle cell lymphoma; MZL: marginal zone lymphoma; WM: Waldenström’s macroglobulinemia; HCL: hairy cell leukemia; FL: follicular lymphoma; BL: Burkitt lymphoma; GCB-DLBCL: germinal-center B-cell-like diffuse large B-cell lymphoma; ABC-DLBCL: activated B-cell-like diffuse large B-cell lymphoma; HL: Hodgkin lymphoma; PMBL: primary mediastinal B-cell lymphoma. AITL: angioimmunoblastic T-cell lymphoma; T-PLL: T-cell prolymphocytic leukemia; LGL: large granular lymphocytic leukemia; MF: mycosis fungoides, SS: Sézary syndrome; ATLL: adult T-cell leukemia/lymphoma; PTCL-NOS: peripheral T-cell lymphoma not otherwise specified; NKTCL: extranodal NK/T-cell lymphoma, nasal-type.
See this image and copyright information in PMC

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