Biomarkers in NHL

Patients with non-Hodgkin's lymphoma (NHL) are in need of better predictive and prognostic markers; this to be able to more accurately inform them in the clinical setting about their likely future and to better inform clinicians and clinician-researchers about treatment decisions. One of the major impediments to the development of such markers in NHL has been the relative lack of access to well-preserved tumor tissue as the bulk of these cancers reside in secondary lymphoid organs. Procurement of tissue from affected lymph nodes for molecular risk stratification only has not yet been adopted as standard clinical practice. One of the ways a biomarker with clinical value in NHL could be developed is through analysis of shed tumor products in plasma or serum from patients carrying NHLs. This is the approach taken by He et al., 2011 in work reported in this issue of Oncotarget [1]. The authors began by developing a clever custom-array-based method to capture and enrich for immunoglobulin heavy chain gene fragments contained in sheared DNA isolated from NHL patients followed by use of massively parallel sequencing to generate a large collection of Ig sequences. Given that tumors usually carry one or two rearranged and often somatically hypermutated Ig allele, the identification of these tumor-specific alleles was possible. The authors demonstrate that they could identify the rearranged Ig genes in primary human NHL-derived DNA and also in paired DNA derived from patient's plasma. They went on to show that they could amplify rearranged Ig fragments from an additional set of NHL patients using just plasma as a source of DNA. To support the analysis of the large collection of DNA sequence tags generated from each sample they developed a set of novel software algorithms for Ig gene identification. In summary, in the majority of patients analyzed the authors were able to identify the tumor-derived Ig sequences and also to enumerate the frequency of these in the input DNA. One of the most important questions related to this innovative work is whether the approach chosen has identified a tumor mass marker in patients with NHL and whether such a features can be clinically exploited. To answer this question, the further development of this potential new biomarker will need to proceed in an organized and logical manner to fully explore its ultimate potential. First, it will be necessary to conduct a new study using a larger collection of paired patient …