Genomic and molecular features distinguish young adult cancer from later-onset cancer

Summary: Young adult cancer has increased in incidence worldwide, but its molecular etiologies remain unclear. We systematically characterize genomic profiles of young adult tumors with ages of onset ≤50 years and compare them to later-onset tumors using over 6,000 cases across 14 cancer types. Whil...

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Autores principales: William Lee, Zishan Wang, Miriam Saffern, Tomi Jun, Kuan-lin Huang
Formato: article
Lenguaje:EN
Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/4600d91da5f646a389cc540603e6c427
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Sumario:Summary: Young adult cancer has increased in incidence worldwide, but its molecular etiologies remain unclear. We systematically characterize genomic profiles of young adult tumors with ages of onset ≤50 years and compare them to later-onset tumors using over 6,000 cases across 14 cancer types. While young adult tumors generally show lower mutation burdens and comparable copy-number variation rates compared to later-onset cases, they are enriched for multiple driver mutations and copy-number alterations in subtype-specific contexts. Characterization of tumor immune microenvironments reveals pan-cancer patterns of elevated TGF-β response/dendritic cells and lower IFN-γ response/macrophages relative to later-onset tumors, corresponding to age-related responses to immunotherapy in several cancer types. Finally, we identify prevalent clinically actionable events that disproportionally affect young adult or later-onset cases. The resulting catalog of age-related molecular drivers can guide precision diagnostics and treatments for young adult cancer.