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Genomic disparities between cancers in adolescent and young adults and in older adults

Author

Listed:
  • Xiaojing Wang

    (UT Health San Antonio
    UT Health San Antonio
    UT Health San Antonio)

  • Anne-Marie Langevin

    (UT Health San Antonio
    UT Health San Antonio)

  • Peter J. Houghton

    (UT Health San Antonio
    UT Health San Antonio
    UT Health San Antonio)

  • Siyuan Zheng

    (UT Health San Antonio
    UT Health San Antonio
    UT Health San Antonio)

Abstract

Cancers cause significant mortality and morbidity in adolescents and young adults (AYAs), but their biological underpinnings are incompletely understood. Here, we analyze clinical and genomic disparities between AYAs and older adults (OAs) in more than 100,000 cancer patients. We find significant differences in clinical presentation between AYAs and OAs, including sex, metastasis rates, race and ethnicity, and cancer histology. In most cancer types, AYA tumors show lower mutation burden and less genome instability. Accordingly, most cancer genes show less mutations and copy number changes in AYAs, including the noncoding TERT promoter mutations. However, CTNNB1 and BRAF mutations are consistently overrepresented in AYAs across multiple cancer types. AYA tumors also exhibit more driver gene fusions that are frequently observed in pediatric cancers. We find that histology is an important contributor to genetic disparities between AYAs and OAs. Mutational signature analysis of hypermutators shows stronger endogenous mutational processes such as MMR-deficiency but weaker exogenous processes such as tobacco exposure in AYAs. Finally, we demonstrate a panoramic view of clinically actionable genetic events in AYA tumors.

Suggested Citation

  • Xiaojing Wang & Anne-Marie Langevin & Peter J. Houghton & Siyuan Zheng, 2022. "Genomic disparities between cancers in adolescent and young adults and in older adults," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34959-2
    DOI: 10.1038/s41467-022-34959-2
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    1. Xinyu Bai & Grace H. Attrill & Tuba N. Gide & Peter M. Ferguson & Kazi J. Nahar & Ping Shang & Ismael A. Vergara & Umaimainthan Palendira & Ines Pires Silva & Matteo S. Carlino & Alexander M. Menzies , 2024. "Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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