Evidence map›Paper›PMID 25096233›Full record

ArticleCancer discovery2014

Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma.

Eliezer M Van Allen, Kent W Mouw, Philip Kim, Gopa Iyer, Nikhil Wagle, Hikmat Al-Ahmadie, Cong Zhu, Irina Ostrovnaya, Gregory V Kryukov, Kevin W O'Connor and 24 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04872036 (Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens), which is not on this map. Cited by 341 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
341citing papers in PubMed, 1 pooled it
40.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04872036 completednot on this map

Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens

TypeobservationalSponsorHellenic Cooperative Oncology GroupRan2000 to 2017Enrolled66ConditionsBladder Cancer
3 · Its place in the literature

Who cites it

341 citing papers in PubMed, 1 synthesis or guideline pooled it, 614 citations in OpenAlex.

  1. Pooled it
  2. Neoadjuvant Nivolumab with or without Ipilimumab for Cisplatin-Ineligible Patients with Muscle-Invasive Bladder Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  4. Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
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281 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 1 institution in 1 country.

Eliezer M Van AllenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Kent W MouwDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Harvard Radiation Oncology Program, Boston, Massachusetts.
Philip KimUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Gopa IyerWeill Cornell Medical College, Cornell University, New York, New York. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Nikhil WagleDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Hikmat Al-AhmadieWeill Cornell Medical College, Cornell University, New York, New York. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Cong ZhuBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Irina OstrovnayaDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Gregory V KryukovBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Kevin W O'ConnorDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
John SfakianosUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Ilana Garcia-GrossmanGenitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Jaegil KimBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Elizabeth A GuancialDivision of Hematology/Oncology, Department of Medicine, University of Rochester Medical Center School of Medicine and Dentistry, Rochester, New York.
Richard BamburyGenitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Samira BahlBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Namrata GuptaBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Deborah FarlowBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Angela QuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Sabina SignorettiDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Justine A BarlettaDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Victor ReuterWeill Cornell Medical College, Cornell University, New York, New York. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Jesse BoehmBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Michael LawrenceBroad Institute of MIT and Harvard, Cambridge, Massachusetts.
Gad GetzBroad Institute of MIT and Harvard, Cambridge, Massachusetts. Massachusetts General Hospital Cancer Center and Department of Pathology, Boston, Massachusetts.
Philip KantoffDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Bernard H BochnerUrology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, Cornell University, New York, New York.
Toni K ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Dean F BajorinWeill Cornell Medical College, Cornell University, New York, New York. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
David B SolitWeill Cornell Medical College, Cornell University, New York, New York. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
Stacey GabrielDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Alan D'AndreaDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Harvard Radiation Oncology Program, Boston, Massachusetts.
Levi A GarrawayDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Broad Institute of MIT and Harvard, Cambridge, Massachusetts. rosenbj1@mskcc.org levi_garraway@dfci.harvard.edu.
Jonathan E RosenbergWeill Cornell Medical College, Cornell University, New York, New York. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. rosenbj1@mskcc.org levi_garraway@dfci.harvard.edu.
Cornell University · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2M
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
The Use of Whole-Exome Sequencing to Guide the Care of Cancer PatientsU01HG006492 · NHGRI · DANA-FARBER CANCER INST · PI JANNE, PASI A, VAN ALLEN, ELIEZER M · 2012 to 2016
$7.3M
UROLOGY ONCOLOGY RESEARCH TRAINING GRANTT32CA082088 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Brett Stewart Carver · 1999 to 2026
$7.1M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA127003NCI NIH HHS T32 CA009172NCI NIH HHS T32 CA082088NHGRI NIH HHS U01 HG006492NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54HG003067
6 · The paper itself

Abstract

unlabelledCisplatin-based chemotherapy is the standard of care for patients with muscle-invasive urothelial carcinoma. Pathologic downstaging to pT0/pTis after neoadjuvant cisplatin-based chemotherapy is associated with improved survival, although molecular determinants of cisplatin response are incompletely understood. We performed whole-exome sequencing on pretreatment tumor and germline DNA from 50 patients with muscle-invasive urothelial carcinoma who received neoadjuvant cisplatin-based chemotherapy followed by cystectomy (25 pT0/pTis "responders," 25 pT2+ "nonresponders") to identify somatic mutations that occurred preferentially in responders. ERCC2, a nucleotide excision repair gene, was the only significantly mutated gene enriched in the cisplatin responders compared with nonresponders (q < 0.01). Expression of representative ERCC2 mutants in an ERCC2-deficient cell line failed to rescue cisplatin and UV sensitivity compared with wild-type ERCC2. The lack of normal ERCC2 function may contribute to cisplatin sensitivity in urothelial cancer, and somatic ERCC2 mutation status may inform cisplatin-containing regimen usage in muscle-invasive urothelial carcinoma. SIGNIFICANCE: Somatic ERCC2 mutations correlate with complete response to cisplatin-based chemosensitivity in muscle-invasive urothelial carcinoma, and clinically identified mutations lead to cisplatin sensitivity in vitro. Nucleotide excision repair pathway defects may drive exceptional response to conventional chemotherapy.

Indexed as

MutationAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCisplatinConserved SequenceDNA RepairDrug Resistance, NeoplasmFemaleHumansMaleMiddle AgedModels, MolecularNeoadjuvant TherapyNeoplasm InvasivenessAntineoplastic AgentsCisplatinXeroderma Pigmentosum Group D Protein

Identifiers

PMID25096233
PMCPMC4238969
OpenAlexW2131178190

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.