The pan-cancer whole-genome landscape of Adolescent and Young Adult solid cancers
- 1Hartwig Medical Foundation
Abstract
Cancer incidence in adolescents and young adults (AYAs; 18-39 years) is rising, but how their tumors differ genomically from those of older adults (OAs) is unclear. We analyzed paired tumor-normal whole-genomes from 698 AYAs and 5,220 OAs, with subcohorts matched by cancer group to disentangle age from tumor type. AYA tumors carried fewer somatic variants yet largely shared the same genetic drivers; many apparent age differences reflected age-dependent cancer subtypes, such as IDH-mutant glioma and HPV-positive cervical cancer. Colibactin, APOBEC and homologous recombination deficiency-associated signatures were more prevalent in AYA colorectal, gynecological and breast cancers, respectively, but were not more mutagenic when present, suggesting earlier-life activity rather than AYA-specific mutagenesis. Tumor type-concordant pathogenic germline variants were enriched in AYAs (10.9% overall versus 6.6% in matched OAs; p=0.006), often with a somatic second hit. Age thus shaped AYA cancer genomes through mutational processes, subtype composition and germline predisposition, supporting comprehensive tumor-normal profiling beyond driver-focused testing.
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BibTeX
@misc{putten2026pancancer,
title = {{The pan-cancer whole-genome landscape of Adolescent and Young Adult solid cancers}},
author = {J. van Putten and A. Rosendahl Huber and R. Koster and S. Roerink and J. de Ligt and P. Roepman and S. Kas and R. van Boxtel and W. van der Graaf and E. Cuppen and H. Nienhuis and The GENAYA consortium},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.759320},
url = {https://www.biorxiv.org/content/10.64898/2026.10.15.759320v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - The pan-cancer whole-genome landscape of Adolescent and Young Adult solid cancers
AU - J. van Putten
AU - A. Rosendahl Huber
AU - R. Koster
AU - S. Roerink
AU - J. de Ligt
AU - P. Roepman
AU - S. Kas
AU - R. van Boxtel
AU - W. van der Graaf
AU - E. Cuppen
AU - H. Nienhuis
AU - The GENAYA consortium
PY - 2026
DA - 2026/10/15
PB - bioRxiv
DO - 10.64898/2026.10.15.759320
UR - https://www.biorxiv.org/content/10.64898/2026.10.15.759320v1
AB - Cancer incidence in adolescents and young adults (AYAs; 18-39 years) is rising, but how their tumors differ genomically from those of older adults (OAs) is unclear. We analyzed paired tumor-normal whole-genomes from 698 AYAs and 5,220 OAs, with subcohorts matched by cancer group to disentangle age from tumor type. AYA tumors carried fewer somatic variants yet largely shared the same genetic drivers; many apparent age differences reflected age-dependent cancer subtypes, such as IDH-mutant glioma and HPV-positive cervical cancer. Colibactin, APOBEC and homologous recombination deficiency-associated signatures were more prevalent in AYA colorectal, gynecological and breast cancers, respectively, but were not more mutagenic when present, suggesting earlier-life activity rather than AYA-specific mutagenesis. Tumor type-concordant pathogenic germline variants were enriched in AYAs (10.9% overall versus 6.6% in matched OAs; p=0.006), often with a somatic second hit. Age thus shaped AYA cancer genomes through mutational processes, subtype composition and germline predisposition, supporting comprehensive tumor-normal profiling beyond driver-focused testing.
ER -