Evidence map›Paper›PMID 27078887›Full record

ArticlePloS one2016

Assessment of Tumor Heterogeneity, as Evidenced by Gene Expression Profiles, Pathway Activation, and Gene Copy Number, in Patients with Multifocal Invasive Lobular Breast Tumors.

Nadine Norton, Pooja P Advani, Daniel J Serie, Xochiquetzal J Geiger, Brian M Necela, Bianca C Axenfeld, Jennifer M Kachergus, Ryan W Feathers, Jennifer M Carr, Julia E Crook and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 19% 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, 38 citations in OpenAlex.

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  9. The clinical significance of receiving a kidney allograft from deceased donor with chronic histologic changes.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021
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  15. Cancers · 2019
    Review
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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

14 authors at 2 institutions in 1 country.

Nadine NortonDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Pooja P AdvaniDivision of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida, United States of America.
Daniel J SerieDepartment of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, United States of America.
Xochiquetzal J GeigerDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, United States of America.
Brian M NecelaDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Bianca C AxenfeldDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Jennifer M KachergusDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Ryan W FeathersDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Jennifer M CarrDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Julia E CrookDepartment of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, United States of America.
Alvaro Moreno-AspitiaDivision of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida, United States of America.
Panos Z AnastasiadisDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Edith A PerezDivision of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida, United States of America.
E Aubrey ThompsonDepartment of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.
Mayo Clinic in Florida · USWinnMed · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundInvasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC.

methodsWe characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue. RNA and DNA were extracted from 3x1.5 mm cores from all foci. Gene expression (730 genes) and copy number (80 genes) were measured using Nanostring PanCancer and Cancer CNV panels. Linear mixed models were employed to compare expression in tumor versus normal samples from the same patient, and to assess heterogeneity (variability) in expression among multiple ILC within an individual.

results35 and 34 genes were upregulated (FC>2) and down-regulated (FC<0.5) respectively in ILC tumor relative to adjacent normal tissue, q<0.05. 9/34 down-regulated genes (FIGF, RELN, PROM1, SFRP1, MMP7, NTRK2, LAMB3, SPRY2, KIT) had changes larger than CDH1, a hallmark of ILC. Copy number changes in these patients were relatively few but consistent across foci within each patient. Amplification of three genes (CCND1, FADD, ORAOV1) at 11q13.3 was present in 2/11 patients in both foci. We observed significant evidence of within-patient between-foci variability (heterogeneity) in gene expression for 466 genes (p<0.05 with FDR 8%), including CDH1, FIGF, RELN, SFRP1, MMP7, NTRK2, LAMB3, SPRY2 and KIT.

conclusionsThere was substantial variation in gene expression between ILC foci within patients, including known markers of ILC, suggesting an additional level of complexity that should be addressed.

Indexed as

TranscriptomeAdultBreastBreast NeoplasmsCarcinoma, LobularChromosomes, Human, Pair 11Cyclin D1DNA, NeoplasmFemaleGene DosageGenetic LociHumansLymphatic MetastasisReelin ProteinRNA, NeoplasmCCND1 protein, humanCyclin D1DNA, NeoplasmReelin ProteinRELN protein, humanRNA, Neoplasm

Identifiers

PMID27078887
PMCPMC4831790
OpenAlexW2341630449

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.