Tissue-of-origin signal in tumour data

The TCGA Pan-Cancer Atlas classification paper found that cell of origin dominates the molecular clustering of ten thousand tumours across thirty-three types. Expression, methylation and even mutation patterns encode the tissue so strongly that a pan-cancer survival or drug-response model gets much of its apparent accuracy from the tissue label; the honest comparison is a tissue-only or cancer-type-only baseline, and within-type (stratified) metrics. The same signal is what classifiers exploit to assign a primary site to cancers of unknown primary (Wikipedia).