*3.4. TRIOBP-4 in Cancer*

In contrast to the general expression of *TRIOBP-1* and, to a lesser extent, longer *TRIOBP* splice variants in cancer [46], *TRIOBP-4* transcripts were specifically seen to be expressed in a cancer cell line, HPAC [45]. Subsequent analysis found TRIOBP-4 to be upregulated in human pancreatic and, to an extent, breast cancer tissue, but not in prostrate or lung cancer tissue. Knockdown of TRIOBP-4 (and longer variants) in several pancreatic cancer cells lines led to a reduction in cell proliferation [45]. Therefore, it appears that TRIOBP-4 may play a specialized role in pancreatic cancer.

Additionally, a T195I missense mutation in TRIOBP-4 was among several mutations detected in a family with seemingly genetic, gastric, and rectal cancer [62]. Subsequent exome sequencing of additional families with these diseases led to the identification of several additional missense mutations in patients, two of which, A660V and S826L, segregated with disease in families [62]. These would also effect longer *TRIOBP* splice forms, and it remains to be confirmed whether they are pathogenic.
