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dc.contributor.authorFoster, H
dc.contributor.authorRuiz, EJ
dc.contributor.authorMoore, C
dc.contributor.authorStamp, GWH
dc.contributor.authorNye, EL
dc.contributor.authorLi, N
dc.contributor.authorPan, Y
dc.contributor.authorHe, Y
dc.contributor.authorDownward, J
dc.contributor.authorBehrens, A
dc.date.accessioned2019-10-30T16:16:52Z
dc.date.issued2019-10
dc.identifier.citationCancer research, 2019, 79 (20), pp. 5159 - 5166
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3395
dc.identifier.eissn1538-7445
dc.identifier.doi10.1158/0008-5472.can-19-0647
dc.description.abstractTumor cells proliferate rapidly and thus are frequently subjected to replication stress and the risk of incomplete duplication of the genome. Fragile sites are replicated late, making them more vulnerable to damage when DNA replication fails to complete. Therefore, genomic alterations at fragile sites are commonly observed in tumors. FRA16D is one of the most common fragile sites in lung cancer, however, the nature of the tumor suppressor genes affected by FRA16D alterations has been controversial. Here, we show that the ATMIN gene, which encodes a cofactor required for activation of ATM kinase by replication stress, is located close to FRA16D and is commonly lost in lung adenocarcinoma. Low ATMIN expression was frequently observed in human lung adenocarcinoma tumors and was associated with reduced patient survival, suggesting that ATMIN functions as a tumor suppressor in lung adenocarcinoma. Heterozygous Atmin deletion significantly increased tumor cell proliferation, tumor burden, and tumor grade in the LSL-KRasG12D; Trp53 F/F (KP) mouse model of lung adenocarcinoma, identifying ATMIN as a haploinsufficient tumor suppressor. ATMIN-deficient KP lung tumor cells showed increased survival in response to replication stress and consequently accumulated DNA damage. Thus, our data identify ATMIN as a key gene affected by genomic deletions at FRA16D in lung adenocarcinoma. SIGNIFICANCE: These findings identify ATMIN as a tumor suppressor in LUAD; fragility at chr16q23 correlates with loss of ATMIN in human LUAD and deletion of Atmin increases tumor burden in a LUAD mouse model.
dc.formatPrint-Electronic
dc.format.extent5159 - 5166
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectCells, Cultured
dc.subjectChromosomes, Human, Pair 16
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectAdenocarcinoma
dc.subjectLung Neoplasms
dc.subjectDNA Damage
dc.subjectTumor Suppressor Proteins
dc.subjectTranscription Factors
dc.subjectTumor Burden
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectGenotype
dc.subjectGenes, Tumor Suppressor
dc.subjectChromosome Fragile Sites
dc.subjectKaplan-Meier Estimate
dc.subjectNeoplasm Grading
dc.title<i>ATMIN</i> Is a Tumor Suppressor Gene in Lung Adenocarcinoma.
dc.typeJournal Article
dcterms.dateAccepted2019-08-26
rioxxterms.versionofrecord10.1158/0008-5472.can-19-0647
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer research
pubs.issue20
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Lung Cancer Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Lung Cancer Group
pubs.publication-statusPublished
pubs.volume79
pubs.embargo.termsNot known
icr.researchteamLung Cancer Groupen_US
dc.contributor.icrauthorDownward, Julian David Harryen
dc.contributor.icrauthorBehrens, Axelen


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