Evidence map›Paper›PMID 31517177›Full record

ArticleJCO precision oncology2019

Expanded analysis of secondary germline findings from matched tumor/normal sequencing identifies additional clinically significant mutations.

E Ileana Dumbrava, L Brusco, M Daniels, C Wathoo, K Shaw, K Lu, X Zheng, L Strong, J Litton, B Arun and 13 more

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

Article in JCO precision oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01772771 (Molecular Testing for the MD Anderson Cancer Center Personalized Cancer Therapy Program), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–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.

NCT01772771 recruitingnot on this map

Molecular Testing for the MD Anderson Cancer Center Personalized Cancer Therapy Program

TypeobservationalSponsorM.D. Anderson Cancer CenterRan2012 to 2033Enrolled12,000ConditionsGlioma, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, MelanomaArmsBiospecimen Collection, Genetic Testing, Medical Chart Review
3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. The breast journal · 2024
    Article
  3. Article
  4. Lung cancer is also a hereditary disease.European respiratory review : an official journal of the European Respiratory Society · 2021
    Review
  5. Review
  6. Article
  7. Article
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

E Ileana DumbravaDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
L BruscoSheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M DanielsDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
C WathooSheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
K ShawSheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
K LuDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
X ZhengDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
L StrongProgram of Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J LittonDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
B ArunProgram of Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
A K EterovicDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M RoutbortDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
K PatelDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yuan QiDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
S Piha-PaulDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
V SubbiahDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
D HongDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J RodonDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
S KopetzDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J MendelsohnSheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
G B MillsSheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
K ChenSheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
F Meric-BernstamDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Paul Calabresi Clinical Oncology AwardK12CA088084 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI David S. Hong, Scott Kopetz · 2000 to 2026
$14.0M
Center for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4M
Informatics to enable routine personalized cancer therapyU01CA180964 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BERNSTAM, ELMER V., MERIC-BERNSTAM, FUNDA · 2013 to 2015
$964k
NCATS NIH HHS UL1 TR000371NCI NIH HHS K12 CA088084NCI NIH HHS P30 CA016672NCI NIH HHS U01 CA180964
6 · The paper itself

Abstract

backgroundNext-generation sequencing (NGS) for tumor molecular profiling can reveal secondary germline pathogenic and likely pathogenic variants (LPV/PV). The American College of Medical Genetics (ACMG) recommends return of secondary results for a subset of 59 genes, but other genes with evidence of clinical utility are emerging. We previously reported that 4.3% of patients who underwent NGS of a targeted panel of 201 genes had LPV/PV based on the ACMG list. Here we report the frequency of additional germline cancer-related gene variants and discuss their clinical utility. PATIENTS AND

methodsMatched tumor and germline DNA NGS of a targeted panel of 201 genes was performed in a research laboratory on samples from 1000 patients with advanced or metastatic solid tumors enrolled in a molecular testing protocol (NCT01772771). The frequency of germline LPV/PV in 54 cancer-related genes, beyond the genes in ACMG list, were analyzed.

resultsAmong 1000 patients who underwent tumor/normal DNA sequencing, 46 (4.6%) were found to have a germline LPV/PV in the following genes:

conclusionsBroader genomic testing is likely to identify additional secondary pathogenic germline alterations, some with potential clinical utility for return to patients and their relatives. The recommended genes for which germline results should be returned are continually changing, warranting continued study.

Indexed as

hereditary cancer-related genesmatched tumor/normal DNAnext-generation sequencingNGSsecondary germline variants

Identifiers

PMID31517177
PMCPMC6741435

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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.