Details

Autor(en) / Beteiligte

• Nguyen, Peter T.
• Coetzee, Simon G.
• Lakeland, Daniel L.
• Hazelett, Dennis J.

Titel

A molecular taxonomy of tumors independent of tissue-of-origin

Ist Teil von

• iScience, 2021-10, Vol.24 (10), p.103084-103084, Article 103084

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Cancer is an organism-level disease, impacting processes from cellular metabolism and the microenvironment to systemic immune response. Nevertheless, efforts to distinguish overarching mutational processes from interactions with the cell of origin for a tumor have seen limited success, presenting a barrier to individualized medicine. Here we present a pathway-centric approach, extracting somatic mutational profiles within and between tissues, largely orthogonal to cell of origin, mutational burden, or stage. Known predisposition variants are equally distributed among clusters, and largely independent of molecular subtype. Prognosis and risk of death vary jointly by cancer type and cluster. Analysis of metastatic tumors reveals that differences are largely cluster-specific and complementary, implicating convergent mechanisms that combine familiar driver genes with diverse low-frequency lesions in tumor-promoting pathways, ultimately producing distinct molecular phenotypes. The results shed new light on the interplay between organism-level dysfunction and tissue-specific lesions. [Display omitted] •Pathway-based clustering is applied to reclassify tumors using somatic mutations•Clusters represent distinct molecular features that cut across tissue-of-origin•Risk of death is modelled using tissue origin and cluster membership Genomics; Bioinformatics; Cancer