Evidence map›Paper›PMID 29897959›Full record

ArticlePloS one2018

Accounting for tumor heterogeneity when using CRISPR-Cas9 for cancer progression and drug sensitivity studies.

Jessica F Olive, Yuanbo Qin, Molly J DeCristo, Tyler Laszewski, Frances Greathouse, Sandra S McAllister

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 34% 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.

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

9 citing papers in PubMed, 17 citations in OpenAlex.

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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

6 authors at 2 institutions in 1 country.

Jessica F OliveDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Yuanbo QinDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Molly J DeCristoDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Tyler LaszewskiDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Frances GreathouseDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Sandra S McAllisterDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.ORCID 0000-0002-5111-5903
Brigham and Women's Hospital · USBroad Institute · US

Funding

Understanding How Breast Cancers Activate and Respond to the Systemic EnvironmentR01CA166284 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI MCALLISTER, SANDRA S · 2012 to 2018
$2.2M
NCI NIH HHS R01 CA166284
6 · The paper itself

Abstract

Gene editing protocols often require the use of a subcloning step to isolate successfully edited cells, the behavior of which is then compared to the aggregate parental population and/or other non-edited subclones. Here we demonstrate that the inherent functional heterogeneity present in many cell lines can render these populations inappropriate controls, resulting in erroneous interpretations of experimental findings. We describe a novel CRISPR/Cas9 protocol that incorporates a single-cell cloning step prior to gene editing, allowing for the generation of appropriately matched, functionally equivalent control and edited cell lines. As a proof of concept, we generated matched control and osteopontin-knockout Her2+ and Estrogen receptor-negative murine mammary carcinoma cell lines and demonstrated that the osteopontin-knockout cell lines exhibit the expected biological phenotypes, including unaffected primary tumor growth kinetics and reduced metastatic outgrowth in female FVB mice. Using these matched cell lines, we discovered that osteopontin-knockout mammary tumors were more sensitive than control tumors to chemotherapy in vivo. Our results demonstrate that heterogeneity must be considered during experimental design when utilizing gene editing protocols and provide a solution to account for it.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCRISPR-Cas SystemsDisease ProgressionErb-b2 Receptor Tyrosine KinasesGene EditingHumansMiceMice, Inbred NODMice, SCIDNeoplasm MetastasisNeoplasmsOsteopontinPhenotypeTransplantation, HeterologousAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesOsteopontin

Identifiers

PMID29897959
PMCPMC5999218
OpenAlexW2808080211

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.