A1 Refereed original research article in a scientific journal
Genome-wide quantification of copy-number aberration impact on gene expression in ovarian high-grade serous carcinoma
Authors: Jamalzadeh Sanaz, Dai Jun, Lavikka Kari, Li Yilin, Jiang Jing, Huhtinen Kaisa, Virtanen Anni, Oikkonen Jaana, Hietanen Sakari, Hynninen Johanna, Vähärautio Anna, Häkkinen Antti, Hautaniemi Sampsa
Publisher: BioMed Central
Publication year: 2024
Journal: BMC Cancer
Journal name in source: BMC CANCER
Journal acronym: BMC CANCER
Article number: 173
Volume: 24
Issue: 1
Number of pages: 14
eISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-024-11895-6
Web address : https://bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11895-6
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/387072749
Copy-number alterations (CNAs) are a hallmark of cancer and can regulate cancer cell states via altered gene expression values. Herein, we have developed a copy-number impact (CNI) analysis method that quantifies the degree to which a gene expression value is impacted by CNAs and leveraged this analysis at the pathway level. Our results show that a high CNA is not necessarily reflected at the gene expression level, and our method is capable of detecting genes and pathways whose activity is strongly influenced by CNAs. Furthermore, the CNI analysis enables unbiased categorization of CNA categories, such as deletions and amplifications. We identified six CNI-driven pathways associated with poor treatment response in ovarian high-grade serous carcinoma (HGSC), which we found to be the most CNA-driven cancer across 14 cancer types. The key driver in most of these pathways was amplified wild-type KRAS, which we validated functionally using CRISPR modulation. Our results suggest that wild-type KRAS amplification is a driver of chemotherapy resistance in HGSC and may serve as a potential treatment target.
Downloadable publication This is an electronic reprint of the original article. |  |
