Authors: Jian He Jian Wu Yuchen Jiao Fausto J Rodriguez Jaishri O Blakeley Kenneth W Kinzler Nickolas Papadopoulos Bert Vogelstein Matthias Holdhoff
Publish Date: 2013/07/05
Volume: 114, Issue: 3, Pages: 275-279
Abstract
Chemotherapybased treatment of patients with primary central nervous system lymphoma can lead to durable remissions and potentially cure in a fraction of patients Accurate assessment of residual disease is necessary to determine the duration and success of treatment that cannot be achieved by contrastenhanced imaging due to limited sensitivity and specificity A tumorderived bloodbased biomarker if detectable and quantifiable could serve as a more specific and reliable marker for these patients The goal of this study was to assess whether lymphomaspecific IgH rearrangements can be detected in plasma of patients with PCNSL PCNSL tissue was analyzed by capturing and sequencing the IgH genomic regions IgCap using next generation sequencing with the Illumina platform Plasma of patients with detected IgH rearrangement was then analyzed for presence of the respective rearrangement using polymerase chain reaction Tumor tissue and matched plasma of five treatmentnaïve patients with biopsyproven PCNSL mean age of 656 years range 62–68 years were analyzed All patients had measurable contrastenhancing disease on MRI at time of plasma collection IgH rearrangements were identified in 4 of 5 analyzed PCNSL tissue samples The respective rearrangement could be detected in the plasma of 1 patient 25 but not in the others IgH rearrangements can be detected in tumor tissue of patients with PCNSL using IgCap however they are absent or only present in minimal quantities in plasma even in treatmentnatïve patients with bulky disease Alternative strategies to develop circulating biomarkers for PCNSL patients need to be exploredThis work was supported by the Robert H Gross Memorial Fund The Virginia and DK Ludwig Fund for Cancer Research and NIH grants CA96888 P01CA015396 and P30CA006973 MH was recipient of a Conquer Cancer Center Young Investigator Award by the American Society of Clinical Oncology We thank Cherie Blair and Katharine Judge for sample acquisition and Dr Stuart A Grossman for critical review of this manuscriptKWK NP and BV are cofounders of Inostics and Personal Genome Diagnostics PGDx own stock and are members of their Scientific Advisory Boards Inostics and PGDx have licensed several patent applications from Johns Hopkins on which KWK NP and BV are inventors
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