Some trans-eQTL hits were significant and may merit further investigation based on previously established biological roles for associated loci, indicating complementary utility of eQTL and that the two methods may be most useful when applied side-by-side. Copy number analysis of this EC dataset by the original authors revealed two regions of gain that were predictive of survival - 3q26.32 and 12p12.1 [27]. Deletions were not considered. Because PIK3CA is located in this region, the authors proposed a role for the PI3-kinase pathway, and found supporting evidence for this theory based on indirect, bioinformatic analysis of existing, in vitro data. Located 200 kb from PIK3CA is ZNF639, a.k.a. ZASC1, which is often contained within the same amplicon in cancer [72,73]. ZNF639 was originally identified in squamous cell carcinoma as a Kruppel-like transcription factor with mRNA expression levels prognostic for survival and metastasis [72,73]. trans-eQTL identified a SNP less than 35 kb upstream of ZNF639 (SNP_A-1686963) driving expression of the TCF12 gene at 15q21. TCF12, a.k.a. HTF4 or ME1, is a basic helix-loop-helix TF with key roles in development [74]. In a
