Notably, loss of a single Smad4 allele in T-cells also resulted in hyperplasia and polyp formation in the intestinal epithelial layer, thus indicating that Smad4 haploinsufficiency plays a causative role in GI tumor formation by exerting a 'landscaping' effect from within the stromal compartment [11]. This evidence concerns the gene SMAD4 and digestive system neoplasm.