SMAD4 and cancer: Furthermore, an analysis of 530 human HNSCC tumors (TCGA, Firehose Head and Neck) using The Cancer Genome Atlas via cBioportal34,35 shows increased TGFB1 mRNA levels in SMAD4-deleted tumors (n = 253) relative to SMAD4 diploid tumors (P = 0.0011, n = 205), and no change in tumors with SMAD4 gain (P = 0.4215, n = 30) (Fig. 1b).