Integrated Analysis of Racial Disparities in Genomic Architecture Identifies a Trans-ancestry Prognostic Subtype in Bladder Cancer

Authors

Baifeng Zhang
Peilin Jia
Jiayin Wang
Guangsheng Pei
Changxi Wang
Shimei Pei
Xiangchun Li
Zhongming Zhao
Xin Yi
Xin-Yuan Guan
Yi Huang

Publication Date

4-1-2023

Journal

Molecular Oncology

Abstract

The incidence of bladder cancer and patient survival vary greatly among different populations, but the influence of the associated molecular features and evolutionary processes on its clinical treatment and prognostication remains unknown. Here, we analyze the genomic architectures of 505 bladder cancer patients from Asian/Black/White populations. We identify a previously unknown association between AHNAK mutations and activity of the APOBEC-a mutational signature, the activity of which varied substantially across populations. All significantly mutated genes but only half of arm-level somatic copy number alterations (SCNAs) are enriched with clonal events, indicating large-scale SCNAs as rich sources of bladder cancer clonal diversities. The prevalence of TP53 and ATM clonal mutations as well as the associated burden of SCNAs is significantly higher in Whites/Blacks than in Asians. We identify a trans-ancestry prognostic subtype of bladder cancer characterized by enrichment of non-muscle-invasive patients and muscle-invasive patients with good prognosis, increased CREBBP/FGFR3/HRAS/NFE2L2 mutations, decreased intra-tumor heterogeneity and genome instability, and an activated tumor microenvironment.

Keywords

Humans, Prognosis, Urinary Bladder Neoplasms, Mutation, Genomic Instability, Genomics, Tumor Microenvironment, bladder cancer, genomic architectures, tumor heterogeneity, tumor microenvironment

DOI

10.1002/1878-0261.13360

PMID

36495164

PMCID

PMC10061287

PubMedCentral® Posted Date

12-29-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes