Evidence map›Paper›PMID 36179682›Full record

ArticleCancer cell2022

Ancestry-driven recalibration of tumor mutational burden and disparate clinical outcomes in response to immune checkpoint inhibitors.

Amin H Nassar, Elio Adib, Sarah Abou Alaiwi, Talal El Zarif, Stefan Groha, Elie W Akl, Pier Vitale Nuzzo, Tarek H Mouhieddine, Tomin Perea-Chamblee, Kodi Taraszka and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Molecular subtypes and survival patterns of endometrial cancer in a South Indian cohort.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026
    Article
  6. Genetic evidence for POR-mediated ferroptosis in lung cancer prevention: a causal role of granulocyte modulation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors.

Amin H NassarDepartment of Hematology/Oncology, Yale New Haven Hospital, New Haven, CT 06510, USA; Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Elio AdibLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Sarah Abou AlaiwiLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Talal El ZarifLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Stefan GrohaDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Elie W AklDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Pier Vitale NuzzoLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Tarek H MouhieddineDivision of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Tomin Perea-ChambleeDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Kodi TaraszkaDepartment of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Habib El-KhouryCenter for Prevention of Progression of Blood Cancers, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Muhieddine LabbanDepartment of Urologic Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Christopher FongDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Kanika S AroraDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Chris LabakiLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Wenxin XuLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Guru SonpavdeLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Robert I HaddadDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kent W MouwDepartment of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Marios GiannakisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
F Stephen HodiMelanoma Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Noah ZaitlenDepartment of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Adam J SchoenfeldThoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 1275 York Avenue, New York, NY 10065, USA.
Nikolaus SchultzDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Michael F BergerDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Laura E MacConaillDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Guruprasad AnandaCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
David J KwiatkowskiDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Toni K ChoueiriLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Deborah SchragDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jian Carrot-ZhangDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Alexander GusevDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: alexander_gusev@dfci.harvard.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Methods for Genome-wide Association Studies in Admixed PopulationsR01HG006399 · NHGRI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI PRICE, ALKES L · 2011 to 2024
$6.3M
Characterizing the evolutionary architecture of complex disease within and across diverse populationsR01HG012133 · NHGRI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MANCUSO, NICHOLAS · 2021 to 2025
$3.6M
(PQ3) A functional genomic approach to identification and interpretation of germline-tumor genetic interactionsR01CA227237 · NCI · DANA-FARBER CANCER INST · PI GUSEV, ALEXANDER, ZAITLEN, NOAH A · 2018 to 2022
$3.5M
Characterizing non-coding somatic and germline variant interactions in ovarian cancerR01CA244569 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GAYTHER, SIMON ANDREW, GUSEV, ALEXANDER · 2020 to 2024
$3.3M
Common biology underlying pleiotropic breast, prostate and ovarian cancer risk lociR01CA259058 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI MATTHEW L FREEDMAN, Simon Andrew Gayther · 2022 to 2026
$2.5M
Understanding Ancestral Contribution to Lung AdenocarcinomaR00CA259223 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ZHANG, JIAN · 2022 to 2024
$738k
NCI NIH HHS P30 CA008748NCI NIH HHS R00 CA259223NCI NIH HHS R01 CA227237NCI NIH HHS R01 CA244569NCI NIH HHS R01 CA259058NHGRI NIH HHS R01 HG006399NHGRI NIH HHS R01 HG012133
6 · The paper itself

Abstract

The immune checkpoint inhibitor (ICI) pembrolizumab is US FDA approved for treatment of solid tumors with high tumor mutational burden (TMB-high; ≥10 variants/Mb). However, the extent to which TMB-high generalizes as an accurate biomarker in diverse patient populations is largely unknown. Using two clinical cohorts, we investigated the interplay between genetic ancestry, TMB, and tumor-only versus tumor-normal paired sequencing in solid tumors. TMB estimates from tumor-only panels substantially overclassified individuals into the clinically important TMB-high group due to germline contamination, and this bias was particularly pronounced in patients with Asian/African ancestry. Among patients with non-small cell lung cancer treated with ICIs, those misclassified as TMB-high from tumor-only panels did not associate with improved outcomes. TMB-high was significantly associated with improved outcomes only in European ancestries and merits validation in non-European ancestry populations. Ancestry-aware tumor-only TMB calibration and ancestry-diverse biomarker studies are critical to ensure that existing disparities are not exacerbated in precision medicine.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsBiomarkers, TumorHumansImmune Checkpoint InhibitorsMutationTumor BurdenBiomarkers, TumorImmune Checkpoint Inhibitorsbiomarkercancer disparitiesgenetic ancestrygenomicsimmunotherapytumor mutational burden

Identifiers

PMID36179682
PMCPMC9559771

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Registered trials

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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.