Toward a Unified Theory of Why Young People Develop Cancer. Review uri icon

Overview

abstract

  • Epidemiologic and genetic studies have now defined specific patterns of incidence and distinct molecular features of cancers in young versus aging people. Here, I review a general framework for the causes of cancer in children and young adults by relating somatic genetic mosaicism and developmental tissue mutagenesis. This framework suggests how aging-associated cancers such as carcinomas, glioblastomas, and myelodysplastic leukemias are causally distinct from cancers that predominantly affect children and young adults, including lymphoblastic and myeloid leukemias, sarcomas, neuroblastomas, medulloblastomas, and other developmental cancers. I discuss the oncogenic activities of known developmental mutators RAG1/2, AID, and PGBD5, and describe strategies needed to define missing developmental causes of young-onset cancers. Thus, a precise understanding of the mechanisms of tissue-specific somatic mosaicism, developmental mutators, and their control by human genetic variation and environmental exposures is needed for improved strategies for cancer screening, prevention, and treatment.

publication date

  • October 1, 2024

Research

keywords

  • Neoplasms

Identity

PubMed Central ID

  • PMC11444251

Scopus Document Identifier

  • 85205603939

Digital Object Identifier (DOI)

  • 10.1101/cshperspect.a041658

PubMed ID

  • 38692742

Additional Document Info

volume

  • 14

issue

  • 10