Intratumoral hypoxia is known to be a trigger for HMGB1 translocation and release [27, 51, 33] and increased expression of HMGB1 receptors [40] Our data support a potential mechanistic relationship between VHL/hypoxia signaling and HMGB1, as VHL mutation in the PDX panel was associated with higher HMGB1 secretion in tumor-bearing mice. The gene discussed is VHL; the disease is neoplasm.