ATM/RB1 mutations predict shorter overall survival in urothelial cancer

Ming Yin, Petros Grivas, Hamid Emamekhoo, Prateek Mendiratta, Siraj Ali, Jo Ann Hsu, Monali Vasekar, Joseph J. Drabick, Sumanta Pal, Monika Joshi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Mutations of DNA repair genes, e.g. ATM/RB1, are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. Results: In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Materials and Methods: Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). Conclusions: ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

Original languageEnglish (US)
Pages (from-to)16891-16898
Number of pages8
JournalOncotarget
Volume9
Issue number24
DOIs
StatePublished - Mar 30 2018

Fingerprint

Mutation
Survival
Neoplasms
Confidence Intervals
Exome
Drug Therapy
Atlases
Platinum
Urinary Bladder Neoplasms
DNA Repair
Immunotherapy
Cisplatin
Biomarkers
Regression Analysis
Genome
Genes
Datasets

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Yin, M., Grivas, P., Emamekhoo, H., Mendiratta, P., Ali, S., Hsu, J. A., ... Joshi, M. (2018). ATM/RB1 mutations predict shorter overall survival in urothelial cancer. Oncotarget, 9(24), 16891-16898. https://doi.org/10.18632/oncotarget.24738
Yin, Ming ; Grivas, Petros ; Emamekhoo, Hamid ; Mendiratta, Prateek ; Ali, Siraj ; Hsu, Jo Ann ; Vasekar, Monali ; Drabick, Joseph J. ; Pal, Sumanta ; Joshi, Monika. / ATM/RB1 mutations predict shorter overall survival in urothelial cancer. In: Oncotarget. 2018 ; Vol. 9, No. 24. pp. 16891-16898.
@article{3c5c4b6fd79643cda8dd1c237bf24c47,
title = "ATM/RB1 mutations predict shorter overall survival in urothelial cancer",
abstract = "Background: Mutations of DNA repair genes, e.g. ATM/RB1, are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. Results: In the discovery dataset, ATM/RB1 mutations were present in 24{\%} of patients and were associated with shorter OS (adjusted HR 2.67, 95{\%} CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2{\%} of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95{\%} CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Materials and Methods: Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95{\%} confidence interval (CI) to compare overall survival (OS). Conclusions: ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.",
author = "Ming Yin and Petros Grivas and Hamid Emamekhoo and Prateek Mendiratta and Siraj Ali and Hsu, {Jo Ann} and Monali Vasekar and Drabick, {Joseph J.} and Sumanta Pal and Monika Joshi",
year = "2018",
month = "3",
day = "30",
doi = "10.18632/oncotarget.24738",
language = "English (US)",
volume = "9",
pages = "16891--16898",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "24",

}

Yin, M, Grivas, P, Emamekhoo, H, Mendiratta, P, Ali, S, Hsu, JA, Vasekar, M, Drabick, JJ, Pal, S & Joshi, M 2018, 'ATM/RB1 mutations predict shorter overall survival in urothelial cancer', Oncotarget, vol. 9, no. 24, pp. 16891-16898. https://doi.org/10.18632/oncotarget.24738

ATM/RB1 mutations predict shorter overall survival in urothelial cancer. / Yin, Ming; Grivas, Petros; Emamekhoo, Hamid; Mendiratta, Prateek; Ali, Siraj; Hsu, Jo Ann; Vasekar, Monali; Drabick, Joseph J.; Pal, Sumanta; Joshi, Monika.

In: Oncotarget, Vol. 9, No. 24, 30.03.2018, p. 16891-16898.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ATM/RB1 mutations predict shorter overall survival in urothelial cancer

AU - Yin, Ming

AU - Grivas, Petros

AU - Emamekhoo, Hamid

AU - Mendiratta, Prateek

AU - Ali, Siraj

AU - Hsu, Jo Ann

AU - Vasekar, Monali

AU - Drabick, Joseph J.

AU - Pal, Sumanta

AU - Joshi, Monika

PY - 2018/3/30

Y1 - 2018/3/30

N2 - Background: Mutations of DNA repair genes, e.g. ATM/RB1, are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. Results: In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Materials and Methods: Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). Conclusions: ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

AB - Background: Mutations of DNA repair genes, e.g. ATM/RB1, are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. Results: In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Materials and Methods: Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). Conclusions: ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=85044724537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044724537&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.24738

DO - 10.18632/oncotarget.24738

M3 - Article

C2 - 29682192

AN - SCOPUS:85044724537

VL - 9

SP - 16891

EP - 16898

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 24

ER -

Yin M, Grivas P, Emamekhoo H, Mendiratta P, Ali S, Hsu JA et al. ATM/RB1 mutations predict shorter overall survival in urothelial cancer. Oncotarget. 2018 Mar 30;9(24):16891-16898. https://doi.org/10.18632/oncotarget.24738