Molecular Fingerprinting of Anatomically and Temporally Distinct B-Cell Lymphoma Samples by Next-Generation Sequencing to Establish Clonal Relatedness

[...]it is unlikely that 2 independent events would share the same genomic breakpoint in both partner genes. [...]we hypothesized that the genomic breakpoints should be the same for successive occurrences of clonally related FL in a single patient and would be expected to differ from one patient with FL to another. Similar cases were reported in a series by Geurts-Giele et al.8 On the other hand, identically sized rearrangements detected in 2 lymphomas by PCR-based methods can also represent 2 unrelated processes when further evaluated by sequencing as shown by Nishiuchi et al16 in 2 of 5 cases studied. [...]published data support the conclusion that relying on the size of the clonal rearrangements to distinguish related from unrelated processes is not a completely reliable method and it should be supplemented by additional investigation. [...]translocations involving MYC or BCL6 are associated with more aggressive disease in FL and have been shown to be a harbinger of transformation.17,18 In particular, concurrent BCL2 and MYC rearrangement is associated with a particularly aggressive clinical course.19 Since a second rearrangement was identified in initial FL samples from these patients, it argues for the use of NGS in lieu of targeted FISH or less sensitive cytogenetics studies at initial diagnosis, since early identification of a second rearrangement can have prognostic and therapeutic significance. In summary we show that an NGS-based method is a superior alternative to currently used methods in determining clonal relationship between distinct tumors. Because NGS as a technique is becoming more widely available and used in clinical practice, the potential to streamline lymphoma workup to a single platform and assay in the near future will provide additional benefit.