And multiple other members the jak-stat signaling pathway

Furthermore, the burden of late-onset therapy-induced toxicities (eg, lung and heart dysfunction, secondary cancers, infertility) is of increasing concern in all patients with cHL receiving chemoradiotherapy at a young age.

Fluorescence in situ hybridization (FISH) for JAK2, TNFAIP3, and B2M.

In summary, our analysis of the cHL coding genome uncovered recurrent mutations in several genes, most notably GNA13, XPO1, ITPKB, STAT6, and multiple other members of the JAK-STAT signaling pathway, pointing to a critical role for these genes in the pathogenesis of cHL.

The high frequency of mutations in JAK-STAT pathway genes provides a genetic explanation for the constitutive activation of this cascade in almost 90% of cases. Although additional studies will be needed to mechanistically document the dependency of the mutated cHL cell lines on the affected genes, the observed association between the presence of specific gene mutations and the susceptibility to targeted pathway inhibition suggests new therapeutic targets in this common lymphoma. Finally, the landscape of recurrently mutated genes we have defined in cHL can be harnessed to develop liquid biopsy strategies for noninvasive monitoring of the response to therapy.66  This could improve the imperfect prognostic accuracy of PET imaging in guiding treatment escalation or de-escalation,67  and thereby reduce the overall toxicity burden associated to chemo-radiotherapy.