CISH and breast cancer: Knowing that SOCS gene promoter hypermethylation is an important mechanism in SOCS gene silencing and subsequent deregulation of the JAK/STAT signaling, Sutherland et al found promoter hypermethylation and silencing of SOCS1 (but not of SOCS2 or SOCS3) to occur in 9% of breast cancers and various degrees of SOCS transcription in several breast carcinoma cell lines, and suggested that silencing of specific SOCS genes in breast, may augment cytokine responsiveness, thereby contributing to oncogenesis [29].