9q22.2

found in Peripheral T-cell lymphoma (Streubel et al. 2006).

N-terminal ITK (bp 1-577) fused in frame with C-terminal SYK cDNA

found in a case of myelodysplastic syndrome (Kuno et al. 2001).

ETV6-SYK is constituvely tyrosine phosphorylated

Breast cancer

SYK mRNA and protein expression in a panel of well-characterized breast cancer cell lines, normal mammary gland tissue, and a normal breast epithelial cell line has been investigated by Coopman et al (Coopman 2000). They readily detected SYK expression in normal mammary tissue and epithelium, as well as in non-invasive breast carcinoma cell lines. SYK expression was however observed to be reduced or absent in the invasive breast tumor cell lines. Hypermethylation of the SYK locus during breast cancer progression was found to cause a loss of SYK protein expression in highly invasive and metastatic human mammary carcinomas (Coopman 2000,Yuan 2001). Moreover, Wang et al have shown that full-length SYK can enter the nucleus and thereby suppress invasion (Wang 2003). The sequences confined to a region of the SYK molecule near the junction of the linker B and catalytic domain were determined to be responsible for its distribution between the nucleus and cytoplasm (Zhou 2006). It was further demonstrated that the distribution of SYK between the nucleus and cytoplasm was regulated by signals sent downstream from the activated BCR and require the receptor-mediated activation of protein kinase C (PKC) and the induction of new protein synthesis.

Colon carcinoma

Expression of the SYK gene in human colon carcinoma cells is known to be suppressed in a p53-dependent manner, an indication that loss of p53 function during tumorigenesis can lead to deregulation of SYK activity (Okamura 1999). As reviewed recently by Krisenko et al,the levels of SYK mRNA in many cancerous tissues, including colon, are higher than in normal corresponding tissue (Krisenko 2015).

Gastric cancer

An inverse correlation between nuclear SYK and lymph node metastasis was observed in gastric cancer patients (Wang 2004).

Ovarian cancer

Ovarian tumors of low malignant grade have low levels of SYK compared to aggressive grades, which have the highest levels (Prinos 2011). Interestingly, when SYK expression was silenced, anchorage-independent growth was inhibited, and apoptosis was induced in SYK-expressing ovarian cancer cells.

Lung cancer

Primary tumors of small cell lung cancer (SCLC) was examined and found to express higher levels of SYK compared to normal alveolar epithelium (reviewed by Krisenko 2015).

Chronic lymphocytic leukemia (CLL)

Both SYK and ZAP70 are present in CLL in B cells and may compete in facilitating BCR signaling (reviewed in Au-Yeung 2009). CLL fall into two classes, an indolent milder form and an aggressive form that is particularly dependent on SYK activity for survival (Buchner 2009).

Diffuse large B-cell lymphoma (DLBCL)

DLBCL can exhibit tonic or chronic signaling from the BCR that results in constitutive phosphorylation of SYK on activation loop tyrosines (Chen 2008). In a study from 2011 by Cheng et al, 44% of DLBCL samples showed elevated levels of phosphorylated SYK (Cheng 2011).

Follicular lymphoma (FL)

Constitutive activation of SYK has been reported in FL, were primary cells are hyperresponsive to BCR engagement as compared to nonmalignant B cells (Leseux 2006; Irish 2006).

Mantle cell lymphoma (MCL)

Constitutive activation of SYK has been reported in MCL as well, with a frequent overexpression of SYK due to gene amplification in both cell lines and primary tumors (Rinaldi 2006).

Marginal zone lymphoma (MZL)

Ruiz-Ballesteros reported upregulation of SYK in splenic MZL, potentially due to downregulation of microRNAs predicted to modulate SYK gene transcription (Ruiz-Ballesteros 2005).

B cell acute lymphocytic leukemia (B-ALL)

B-ALL cells are derived from pro-B cells that lack pre-BCR or BCR complexes, but still these cells have elevated levels of constitutively active phosphorylated SYK (Perova 2014).

Rheumatoid arthritis (RA)

It is likely that SYK is widely expressed in a range of haemopoietic cell lineages in RA synovium. Inhibition of Syk suppresses both inflammation and bone erosion in animal models of RA (Singh Najjar 2014). Indeed, Syk has been shown to be necessary for emerging pathology in several animal models of arthritis.