Genetic inactivation of both β2-microglobulin and CD58 allows diffuse large B cell lymphoma to evade the immune system, report Columbia University researchers in Cancer Cell. The researchers found that, in 29 percent of cases, the β2-microglobulin gene is inactivated by mutations and deletions — preventing recognition by CD8+ cytotoxic T cells — and, in 21 percent of cases, the CD58 gene is mutated or deleted — affecting immune responses mediated by T and natural killer cells.
A team led by Yale University School of Medicine's Marcus Bosenberg found that Wnt signaling regulates metastasis in Braf-activated Pten-deficient melanoma. Wnt signaling, the authors note, is known to be dysregulated in melanoma. In a mouse model of Braf-activated Pten-deficient melanoma, they altered β-catenin levels, a part of the Wnt pathway, and from this, Bosenberg and his team found that β-catenin mediate metastases to the lymph nodes and lungs.
Finally, Harvard's Matija Snuderl et al. report in Cancer Cell on an example of tumor heterogeneity, which affects tumor growth and progression as well as tumor response to therapy. In glioblastoma, they saw three receptor tyrosine kinases — EGFR, MET, PDGFRA — amplified in different subclones of the tumor. "Each subpopulation was actively dividing, and the genetic changes resulted in protein production, and coexisting subpopulations shared common early genetic mutations indicating their derivation from a single precursor cell," Matija Snuderl et al. say. "The stable coexistence of different clones within the same tumor will have important clinical implications for tumor resistance to targeted therapies."