Mar 20, 2020

Cellular mRNA signals in human kidney tumors

Matthew D YoungSam Behjati


Tumor cells may produce many of the same messenger RNAs (mRNA) as the cell they derive from. The relative abundance of these mRNAs, the transcriptiomic profile, may provide clues into the origin and development of tumors. Here we investigated the cellular origins of 1,300 childhood and adult renal tumors, spanning 7 different subtypes. We decomposed tumor bulk transcriptomes into single cell components, measuring the abundance of single cell derived reference "cellular signals" in each tumor. We quantified the extent to which each tumor utilized fetal cellular signals, finding that all childhood renal tumors are definitively fetal. This replaces the long-held presumption of "fetalness" with a precise, quantitative readout of immaturity. Analyzing cellular signals in each tumor type, we recapitulated previous findings for some, whilst providing novel insights into other, less well understood tumor types. For example, our analyses predicted fetal interstitial cells as the cell of origin of the infant kidney tumor, congenital mesoblastic nephroma, and demonstrate that another childhood kidney cancer, malignant rhabdoid tumor, arises from mesodermally derived cells in early development. We found remarkable uniformity in the cell si...Continue Reading

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Mentioned in this Paper

Interstitial Cell
Profile (Lab Procedure)
Renal Carcinoma
RNA, Messenger
Rhabdoid Tumor

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