See article, p. 216.

Clonal hematopoiesis of in-determinate potential (CHIP) carries increased risk of hematologic malignancy and harbors oncogenic driver mutations. Variant allele frequencies (VAF) determined by bulk sequencing suggest CHIP is common in lymphoma. It remains unclear whether CHIP is a preneoplastic state directly progressing to malignancy, promotes lymphomagenesis through shaping the microenvironment, or contains independently coexisting clones. This study dissects clonal composition within the tumor by laser-capture microdissection of classical Hodgkin lymphoma (cHL) cells and their lymph node microenvironment. The five characterized cases encompass all of these scenarios. In some cases, mutations are found exclusively in lymphoma cells; in others, they are shared with the microenvironment. In two cases, cHL cells exist within clonal territories of nonmalignant cells with different genetic lesions, demonstrating that an expanded clone with oncogenic mutation may coexist with lymphoma rather than initiate it. By combining these data with blood VAF for the...

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