PMCID
PMC13136893

Sensitive detection of somatic mutations in GC-rich cancer gene promoters.

NAR cancer
Authors
Abstract

Somatic mutations in protein-coding genes and noncoding regulatory regions are the major drivers of cancer. Only a relatively small number of somatic noncoding mutations that are likely drivers have been described to date, including those in the promoters of the , and  genes. The impact of these alterations can be profound by initiating, increasing, or abolishing gene expression. Promoter mutations in particular have been difficult to identify even from whole tumor genomes due to their high content of G and C nucleotides, which leads to loss of sequencing coverage in these regions. Therefore, the landscape of somatic drivers in gene promoters remains incomplete. Here, we present a hybrid capture assay optimized for >3000 promoters of cancer genes. We show that this assay allows for deep sequencing of challenging GC-rich promoter regions, enabling discovery of reliable point mutations, short insertions and deletions, copy number variants, and mutational signatures in cell line models as well as formalin-fixed, paraffin-embedded archival tissue samples. Our assay nominated candidate noncoding driver mutations in , and  in breast cancer for future functional follow-up.

Year of Publication
2026
Journal
NAR cancer
Volume
8
Issue
2
Pages
zcag011
Date Published
06/2026
ISSN
2632-8674
DOI
10.1093/narcan/zcag011
PubMed ID
42088607
Links