Show simple item record

dc.contributor.authorRashid, M
dc.contributor.authorvan der Horst, M
dc.contributor.authorMentzel, T
dc.contributor.authorButera, F
dc.contributor.authorFerreira, I
dc.contributor.authorPance, A
dc.contributor.authorRütten, A
dc.contributor.authorLuzar, B
dc.contributor.authorMarusic, Z
dc.contributor.authorde Saint Aubain, N
dc.contributor.authorKo, JS
dc.contributor.authorBillings, SD
dc.contributor.authorChen, S
dc.contributor.authorAbi Daoud, M
dc.contributor.authorHewinson, J
dc.contributor.authorLouzada, S
dc.contributor.authorHarms, PW
dc.contributor.authorCerretelli, G
dc.contributor.authorRobles-Espinoza, CD
dc.contributor.authorPatel, RM
dc.contributor.authorvan der Weyden, L
dc.contributor.authorBakal, C
dc.contributor.authorHornick, JL
dc.contributor.authorArends, MJ
dc.contributor.authorBrenn, T
dc.contributor.authorAdams, DJ
dc.date.accessioned2020-06-03T14:24:46Z
dc.date.issued2019-05-17
dc.identifier.citationNature communications, 2019, 10 (1), pp. 2213 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3696
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-019-09979-0
dc.description.abstractSpiradenoma and cylindroma are distinctive skin adnexal tumors with sweat gland differentiation and potential for malignant transformation and aggressive behaviour. We present the genomic analysis of 75 samples from 57 representative patients including 15 cylindromas, 17 spiradenomas, 2 cylindroma-spiradenoma hybrid tumors, and 24 low- and high-grade spiradenocarcinoma cases, together with morphologically benign precursor regions of these cancers. We reveal somatic or germline alterations of the CYLD gene in 15/15 cylindromas and 5/17 spiradenomas, yet only 2/24 spiradenocarcinomas. Notably, we find a recurrent missense mutation in the kinase domain of the ALPK1 gene in spiradenomas and spiradenocarcinomas, which is mutually exclusive from mutation of CYLD and can activate the NF-κB pathway in reporter assays. In addition, we show that high-grade spiradenocarcinomas carry loss-of-function TP53 mutations, while cylindromas may have disruptive mutations in DNMT3A. Thus, we reveal the genomic landscape of adnexal tumors and therapeutic targets.
dc.formatElectronic
dc.format.extent2213 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectSweat Glands
dc.subjectHumans
dc.subjectCarcinoma, Adenoid Cystic
dc.subjectSweat Gland Neoplasms
dc.subjectProtein Kinases
dc.subjectCohort Studies
dc.subjectDNA Mutational Analysis
dc.subjectMutation, Missense
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectTumor Suppressor Protein p53
dc.subjectProtein Domains
dc.subjectWhole Exome Sequencing
dc.subjectLoss of Function Mutation
dc.subjectDeubiquitinating Enzyme CYLD
dc.subjectDNA (Cytosine-5-)-Methyltransferases
dc.titleALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma.
dc.typeJournal Article
dcterms.dateAccepted2019-04-08
rioxxterms.versionofrecord10.1038/s41467-019-09979-0
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-05-17
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
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/Dynamical Cell Systems
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
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/Dynamical Cell Systems
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.publication-statusPublished
pubs.volume10
pubs.embargo.termsNot known
icr.researchteamDynamical Cell Systemsen_US
dc.contributor.icrauthorButera, Francescaen
dc.contributor.icrauthorBakal, Christopheren


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0