Evidence map›Paper›PMID 30905849›Full record

ArticleEBioMedicine2019

Genomic landscape of allelic imbalance in premalignant atypical adenomatous hyperplasias of the lung.

Smruthy Sivakumar, F Anthony San Lucas, Yasminka A Jakubek, Tina L McDowell, Wenhua Lang, Noah Kallsen, Shanna Peyton, Gareth E Davies, Junya Fukuoka, Yasushi Yatabe and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Smruthy SivakumarDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.
F Anthony San LucasDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yasminka A JakubekDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Tina L McDowellDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Wenhua LangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Noah KallsenAvera Institute for Human Genetics, Sioux Falls, SD, USA.
Shanna PeytonAvera Institute for Human Genetics, Sioux Falls, SD, USA.
Gareth E DaviesAvera Institute for Human Genetics, Sioux Falls, SD, USA.
Junya FukuokaGraduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Yasushi YatabeDepartment of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.
Jianjun ZhangDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
P Andrew FutrealDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jerry FowlerDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Junya FujimotoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Erik A EhliAvera Institute for Human Genetics, Sioux Falls, SD, USA.
Ernest T HawkDivision of Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ignacio I WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Humam KadaraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: hkadara@mdanderson.org.
Paul ScheetDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: pscheet@alum.wustl.edu.
The University of Texas MD Anderson Cancer Center · USAvera Health · USAichi Cancer Center · JPNagasaki University · JP

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundGenomic investigation of atypical adenomatous hyperplasia (AAH), the only known precursor lesion to lung adenocarcinomas (LUAD), presents challenges due to the low mutant cell fractions. This necessitates sensitive methods for detection of chromosomal aberrations to better study the role of critical alterations in early lung cancer pathogenesis and the progression from AAH to LUAD.

methodsWe applied a sensitive haplotype-based statistical technique to detect chromosomal alterations leading to allelic imbalance (AI) from genotype array profiling of 48 matched normal lung parenchyma, AAH and tumor tissues from 16 stage-I LUAD patients. To gain insights into shared developmental trajectories among tissues, we performed phylogenetic analyses and integrated our results with point mutation data, highlighting significantly-mutated driver genes in LUAD pathogenesis.

findingsAI was detected in nine AAHs (56%). Six cases exhibited recurrent loss of 17p. AI and the enrichment of 17p events were predominantly identified in patients with smoking history. Among the nine AAH tissues with detected AI, seven exhibited evidence for shared chromosomal aberrations with matched LUAD specimens, including losses harboring tumor suppressors on 17p, 8p, 9p, 9q, 19p, and gains encompassing oncogenes on 8q, 12p and 1q.

interpretationChromosomal aberrations, particularly 17p loss, appear to play critical roles early in AAH pathogenesis. Genomic instability in AAH, as well as truncal chromosomal aberrations shared with LUAD, provide evidence for mutation accumulation and are suggestive of a cancerized field contributing to the clonal selection and expansion of these premalignant lesions. FUND: Supported in part by Cancer Prevention and Research Institute of Texas (CPRIT) grant RP150079 (PS and HK), NIH grant R01HG005859 (PS) and The University of Texas MD Anderson Cancer Center Core Support Grant.

Indexed as

AdenocarcinomaAdultAgedAged, 80 and overAllelesAllelic ImbalanceCell Transformation, NeoplasticChromosomal InstabilityDisease ProgressionFemaleGenetic HeterogeneityGenome-Wide Association StudyHaplotypesHumansHyperplasiaLungAllelic imbalanceAtypical adenomatous hyperplasiaChromosomal instabilityLung adenocarcinomaPathogenesisPreneoplasia

Identifiers

PMID30905849
PMCPMC6491940
OpenAlexW2922916833

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.