Molecular footprints of muscle-invasive bladder cancer in smoking and nonsmoking patients

Damiano Fantini, Roland Seiler, Joshua J Meeks*

*Corresponding author for this work

Research output: Contribution to journalReview article

Abstract

Background: Bladder cancer is the fifth most common cancer in the United States and smoking is the largest known risk factor. Tobacco-derived carcinogens may induce the accumulation of somatic mutations in urothelial cells, and likely promote tumorigenesis. However, it is still unknown whether smoking-induced bladder carcinogenesis results in tumors with distinctive molecular features that can be therapeutically exploited. Methods: We investigated the genomic alterations of human bladder cancer and examined their association with patient smoking history. We performed bioinformatic analyses and looked at differences in gene expression, somatic mutations, and DNA mutational signatures comparing nonsmokers, reformed smokers, and current smokers. Results: We detected a limited set of gene expression and gene mutation differences between smokers and nonsmokers. We also identified a specific mutational signature that is enriched in tumors from smokers. This mutational signature was described before and has been linked to specific DNA repair defects in human bladder tumors, as well as to the direct effect of nitrosamine carcinogens in the BBN murine model of bladder cancer. Conclusion: We showed associations between smoking status and selected mutational signatures, which could provide insights in the biology of bladder carcinogenesis and tumor progression.

Original languageEnglish (US)
Pages (from-to)818-825
Number of pages8
JournalUrologic Oncology: Seminars and Original Investigations
Volume37
Issue number11
DOIs
StatePublished - Nov 1 2019

Fingerprint

Urinary Bladder Neoplasms
Smoking
Muscles
Carcinogenesis
Carcinogens
Gene Expression
Nitrosamines
Neoplasms
Mutation
Computational Biology
DNA Repair
Tobacco
Urinary Bladder
History
DNA
Genes

Keywords

  • APOBEC mutagenesis
  • BBN mouse model
  • Bladder cancer
  • Cancer genome
  • Mutational signatures
  • Smoking-related carcinogenesis

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

@article{9fe6518877454304b7f3457b79d77e5e,
title = "Molecular footprints of muscle-invasive bladder cancer in smoking and nonsmoking patients",
abstract = "Background: Bladder cancer is the fifth most common cancer in the United States and smoking is the largest known risk factor. Tobacco-derived carcinogens may induce the accumulation of somatic mutations in urothelial cells, and likely promote tumorigenesis. However, it is still unknown whether smoking-induced bladder carcinogenesis results in tumors with distinctive molecular features that can be therapeutically exploited. Methods: We investigated the genomic alterations of human bladder cancer and examined their association with patient smoking history. We performed bioinformatic analyses and looked at differences in gene expression, somatic mutations, and DNA mutational signatures comparing nonsmokers, reformed smokers, and current smokers. Results: We detected a limited set of gene expression and gene mutation differences between smokers and nonsmokers. We also identified a specific mutational signature that is enriched in tumors from smokers. This mutational signature was described before and has been linked to specific DNA repair defects in human bladder tumors, as well as to the direct effect of nitrosamine carcinogens in the BBN murine model of bladder cancer. Conclusion: We showed associations between smoking status and selected mutational signatures, which could provide insights in the biology of bladder carcinogenesis and tumor progression.",
keywords = "APOBEC mutagenesis, BBN mouse model, Bladder cancer, Cancer genome, Mutational signatures, Smoking-related carcinogenesis",
author = "Damiano Fantini and Roland Seiler and Meeks, {Joshua J}",
year = "2019",
month = "11",
day = "1",
doi = "10.1016/j.urolonc.2018.09.017",
language = "English (US)",
volume = "37",
pages = "818--825",
journal = "Urologic Oncology",
issn = "1078-1439",
publisher = "Elsevier Inc.",
number = "11",

}

Molecular footprints of muscle-invasive bladder cancer in smoking and nonsmoking patients. / Fantini, Damiano; Seiler, Roland; Meeks, Joshua J.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 37, No. 11, 01.11.2019, p. 818-825.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Molecular footprints of muscle-invasive bladder cancer in smoking and nonsmoking patients

AU - Fantini, Damiano

AU - Seiler, Roland

AU - Meeks, Joshua J

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Background: Bladder cancer is the fifth most common cancer in the United States and smoking is the largest known risk factor. Tobacco-derived carcinogens may induce the accumulation of somatic mutations in urothelial cells, and likely promote tumorigenesis. However, it is still unknown whether smoking-induced bladder carcinogenesis results in tumors with distinctive molecular features that can be therapeutically exploited. Methods: We investigated the genomic alterations of human bladder cancer and examined their association with patient smoking history. We performed bioinformatic analyses and looked at differences in gene expression, somatic mutations, and DNA mutational signatures comparing nonsmokers, reformed smokers, and current smokers. Results: We detected a limited set of gene expression and gene mutation differences between smokers and nonsmokers. We also identified a specific mutational signature that is enriched in tumors from smokers. This mutational signature was described before and has been linked to specific DNA repair defects in human bladder tumors, as well as to the direct effect of nitrosamine carcinogens in the BBN murine model of bladder cancer. Conclusion: We showed associations between smoking status and selected mutational signatures, which could provide insights in the biology of bladder carcinogenesis and tumor progression.

AB - Background: Bladder cancer is the fifth most common cancer in the United States and smoking is the largest known risk factor. Tobacco-derived carcinogens may induce the accumulation of somatic mutations in urothelial cells, and likely promote tumorigenesis. However, it is still unknown whether smoking-induced bladder carcinogenesis results in tumors with distinctive molecular features that can be therapeutically exploited. Methods: We investigated the genomic alterations of human bladder cancer and examined their association with patient smoking history. We performed bioinformatic analyses and looked at differences in gene expression, somatic mutations, and DNA mutational signatures comparing nonsmokers, reformed smokers, and current smokers. Results: We detected a limited set of gene expression and gene mutation differences between smokers and nonsmokers. We also identified a specific mutational signature that is enriched in tumors from smokers. This mutational signature was described before and has been linked to specific DNA repair defects in human bladder tumors, as well as to the direct effect of nitrosamine carcinogens in the BBN murine model of bladder cancer. Conclusion: We showed associations between smoking status and selected mutational signatures, which could provide insights in the biology of bladder carcinogenesis and tumor progression.

KW - APOBEC mutagenesis

KW - BBN mouse model

KW - Bladder cancer

KW - Cancer genome

KW - Mutational signatures

KW - Smoking-related carcinogenesis

UR - http://www.scopus.com/inward/record.url?scp=85056347977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056347977&partnerID=8YFLogxK

U2 - 10.1016/j.urolonc.2018.09.017

DO - 10.1016/j.urolonc.2018.09.017

M3 - Review article

C2 - 30446446

AN - SCOPUS:85056347977

VL - 37

SP - 818

EP - 825

JO - Urologic Oncology

JF - Urologic Oncology

SN - 1078-1439

IS - 11

ER -