Evidence map›Paper›PMID 28190247›Full record

ArticleBreast cancer research and treatment2017

PIK3CA mutations and TP53 alterations cooperate to increase cancerous phenotypes and tumor heterogeneity.

Sarah Croessmann, Hong Yuen Wong, Daniel J Zabransky, David Chu, D Marc Rosen, Justin Cidado, Rory L Cochran, W Brian Dalton, Bracha Erlanger, Karen Cravero and 5 more

Open access · greenAbstract read
In one paragraph

Article in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 32% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Distinct and convergent effects ofProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Rat somatic genome editing enables ER+ breast cancer modeling.bioRxiv : the preprint server for biology · 2025
    Article
  8. Review
  9. Review
  10. ConcomitantJournal of breast cancer · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Current oncology (Toronto, Ont.) · 2022
    Article
  15. Oncotarget · 2022
    Article
  16. Evaluation of twoMolecular therapy. Methods & clinical development · 2021
    Article
  17. Article
  18. Article
  19. Article
  20. Article
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

15 authors at 2 institutions in 1 country.

Sarah CroessmannThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Hong Yuen WongThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Daniel J ZabranskyThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
David ChuThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
D Marc RosenThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Justin CidadoThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Rory L CochranThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
W Brian DaltonThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Bracha ErlangerThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Karen CraveroThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Berry ButtonThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Kelly Kyker-SnowmanThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Paula J HurleyThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Josh LauringThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA.
Ben Ho ParkThe Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, 1650 Orleans Street, Room 151, Baltimore, MD, 21287, USA. bpark2@jhmi.edu.
Johns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
ONCOLOGY: CHEMOTHERAPY, IMMUNOLOGY, BIOLOGYT32CA009071 · NCI · JOHNS HOPKINS UNIVERSITY · PI Mary Y Armanios, Nilofer S. Azad · 1985 to 2026
$12.8M
Training Program in Cellular and Molecular MedicineT32GM008752 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI RAO, RAJINI · 2000 to 2019
$11.7M
Predoctoral Training Program in Human GeneticsT32GM007814 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 1985 to 2021
$10.6M
Cooperation of Mutant TP53 and PIK3CA in Breast CarcinogensisF31CA167939 · NCI · JOHNS HOPKINS UNIVERSITY · PI CROESSMANN, SARAH E · 2013 to 2015
$88k
A novel model system for risk assessment of BRCA carriersF31CA168180 · NCI · JOHNS HOPKINS UNIVERSITY · PI COCHRAN, RORY LANDON · 2012 to 2013
$84k
NCI NIH HHS F31 CA167939NCI NIH HHS F31 CA168180NCI NIH HHS P30 CA006973NCI NIH HHS T32 CA009071NIGMS NIH HHS T32 GM007309NIGMS NIH HHS T32 GM007814NIGMS NIH HHS T32 GM008752
6 · The paper itself

Abstract

background/purposeThe combined contributions of oncogenes and tumor suppressor genes toward carcinogenesis remain poorly understood. Elucidation of cancer gene cooperativity can provide new insights leading to more effective use of therapies. EXPERIMENTAL DESIGN/

methodsWe used somatic cell genome editing to introduce singly and in combination PIK3CA mutations (E545K or H1047R) with TP53 alterations (R248W or knockout), to assess any enhanced cancerous phenotypes. The non-tumorigenic human breast epithelial cell line, MCF10A, was used as the parental cell line, and resultant cells were assessed via various in vitro assays, growth as xenografts, and drug sensitivity assays using targeted agents and chemotherapies.

resultsCompared to single-gene-targeted cells and parental controls, cells with both a PIK3CA mutation and TP53 alteration had increased cancerous phenotypes including cell proliferation, soft agar colony formation, aberrant morphology in acinar formation assays, and genomic heterogeneity. Cells also displayed varying sensitivities to anti-neoplastic drugs, although all cells with PIK3CA mutations showed a relative increased sensitivity to paclitaxel. All cell lines remained non-tumorigenic.

conclusionsThis cell line panel provides a resource for further elucidating cooperative genetic mediators of carcinogenesis and response to therapies.

Indexed as

MutationPhenotypeAnimalsBreast NeoplasmsCell CycleCell Line, TumorCell ProliferationCentromereClass I Phosphatidylinositol 3-KinasesDisease Models, AnimalDNA Copy Number VariationsDrug Resistance, NeoplasmFemaleGene AmplificationGene EditingGene Knockout TechniquesClass I Phosphatidylinositol 3-KinasesPaclitaxelPIK3CA protein, humanTumor Suppressor Protein p53Breast cancerPIK3CATP53Tumor heterogeneity

Identifiers

PMID28190247
PMCPMC6100768
OpenAlexW2586611056

What OpenQuestion holds

Textmetadata
LicenceTDM
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.