Evidence map›Paper›PMID 25385739›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014

Identification of independent primary tumors and intrapulmonary metastases using DNA rearrangements in non-small-cell lung cancer.

Stephen J Murphy, Marie-Christine Aubry, Faye R Harris, Geoffrey C Halling, Sarah H Johnson, Simone Terra, Travis M Drucker, Michael K Asiedu, Benjamin R Kipp, Eunhee S Yi and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 2 pooled it
9.9field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.

  1. Pooled it
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  6. Lung metastases.Nature reviews. Disease primers · 2025
    Review
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Stephen J MurphyAll authors: Mayo Clinic, Rochester, MN.
Marie-Christine AubryAll authors: Mayo Clinic, Rochester, MN.
Faye R HarrisAll authors: Mayo Clinic, Rochester, MN.
Geoffrey C HallingAll authors: Mayo Clinic, Rochester, MN.
Sarah H JohnsonAll authors: Mayo Clinic, Rochester, MN.
Simone TerraAll authors: Mayo Clinic, Rochester, MN.
Travis M DruckerAll authors: Mayo Clinic, Rochester, MN.
Michael K AsieduAll authors: Mayo Clinic, Rochester, MN.
Benjamin R KippAll authors: Mayo Clinic, Rochester, MN.
Eunhee S YiAll authors: Mayo Clinic, Rochester, MN.
Tobias PeikertAll authors: Mayo Clinic, Rochester, MN.
Ping YangAll authors: Mayo Clinic, Rochester, MN.
George VasmatzisAll authors: Mayo Clinic, Rochester, MN. vasmatzis.george@mayo.edu.
Dennis A WigleAll authors: Mayo Clinic, Rochester, MN.
Mayo Clinic · USWinnMed · USUniversity of Minnesota Rochester · US

Funding

Health and QOL among Long-Term Lung Cancer SurvivorsR01CA115857 · NCI · MAYO CLINIC ROCHESTER · PI YANG, PING · 2006 to 2010
$2.4M
Anti-Tumor Immunity in Response to a Modified Vaccine Strain Measles VirusK23CA159391 · NCI · MAYO CLINIC ROCHESTER · PI PEIKERT, TOBIAS · 2012 to 2015
$657k
NCI NIH HHS K23 CA159391NCI NIH HHS R01 CA115857
6 · The paper itself

Abstract

purposeDistinguishing independent primary tumors from intrapulmonary metastases in non-small-cell carcinoma remains a clinical dilemma with significant clinical implications. Using next-generation DNA sequencing, we developed a chromosomal rearrangement-based approach to differentiate multiple primary tumors from metastasis.

methodsTumor specimens from patients with known independent primary tumors and metastatic lesions were used for lineage test development, which was then applied to multifocal tumors. Laser capture microdissection was performed separately for each tumor. Genomic DNA was isolated using direct in situ whole-genome amplification methodology, and next-generation sequencing was performed using an Illumina mate-pair library protocol. Sequence reads were mapped to the human genome, and primers spanning the fusion junctions were used for validation polymerase chain reaction.

resultsA total of 41 tumor samples were sequenced (33 adenocarcinomas [ADs] and eight squamous cell carcinomas [SQCCs]), with a range of three to 276 breakpoints per tumor identified. Lung tumors predicted to be independent primary tumors based on different histologic subtype did not share any genomic rearrangements. In patients with lung primary tumors and paired distant metastases, shared rearrangements were identified in all tumor pairs, emphasizing the patient specificity of identified breakpoints. Multifocal AD and SQCC samples were reviewed independently by two pulmonary pathologists. Concordance between histology and genomic data occurred in the majority of samples. Discrepant tumor samples were resolved by genome sequencing.

conclusionA diagnostic lineage test based on genomic rearrangements from mate-pair sequencing demonstrates promise for distinguishing independent primary from metastatic disease in lung cancer.

Indexed as

Gene RearrangementCarcinoma, Non-Small-Cell LungGene DosageHumansLaser Capture MicrodissectionLung NeoplasmsSequence Analysis, DNA

Identifiers

PMID25385739
PMCPMC4879716
OpenAlexW2147562944

What OpenQuestion holds

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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.