The origins of seven kidney cancer types, including rare subtypes, have been identified, confirming they originate in specific forms of developmental cells in the foetus.
A study published today in Nature Communications used computational methods to analyse existing datasets and pinpoint the cellular signals given off by different cancers as they emerge.
The researchers, from the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH), UK, the Princess Máxima Centre for Paediatric Oncology, the Netherlands, and Oncode Institute, Netherlands, believe this method is promising as a tool for diagnosing patients with rare cancers after one patient’s cryptic kidney cancer was identified as a Wilms-like tumour after they looked at its cellular signals.
In this study, the research teams used Human Cell Atlas (HCA) reference data and databases of tumour gene expression to assess mRNA signals in 1,300 childhood and adult renal tumours, spanning seven different tumour types.
Their analysis confirmed these childhood cancers are developmental in origin, occurring after errors in a particular developmental cell type’s journey to maturity.
In contrast, most adult kidney cancers emerged from mature cell types and do not revert to a developmental pattern of gene expression.
The researchers found each cancer type exhibited unique cellular signals that could be used to classify them in future.
The study also revealed the behaviour and origins of four kidney tumour subtypes – congenital mesoblastic nephroma, clear cell sarcoma of the kidney, malignant rhabdoid tumour of the kidney, and chromophobe renal cell carcinoma – whose rarity would have made it difficult to examine otherwise.
First author Dr Matthew , from the Wellcome Sanger Institute, said: “It has long been assumed that childhood tumours have ‘foetal’ origins. Now we can replace that loose definition with a precise, quantitative measurement of the cellular signals that different tumour types exhibit.
“Our analysis also refutes the theory that adult tumours revert to a developmental state, unless they are a highly lethal subtype of adult kidney cancer.”
Senior author Dr Sam Behjati, from the Wellcome Sanger Institute, added: “Not only does this computational approach using existing datasets validate previous results on the origins of childhood kidney cancers, it provides a new way of expanding this research to much larger numbers of tumours and rare cancer types.
“I believe that the success of this approach could act as a blueprint for investigating the behaviour and origins of the entire spectrum of human cancer.”
Young MD, Mitchell TD, Custers L et al. Single cell derived mRNA signals across human kidney tumors. Nature Communications 24 June 2021
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