dc.contributor.author | Rashid, M | |
dc.contributor.author | van der Horst, M | |
dc.contributor.author | Mentzel, T | |
dc.contributor.author | Butera, F | |
dc.contributor.author | Ferreira, I | |
dc.contributor.author | Pance, A | |
dc.contributor.author | Rütten, A | |
dc.contributor.author | Luzar, B | |
dc.contributor.author | Marusic, Z | |
dc.contributor.author | de Saint Aubain, N | |
dc.contributor.author | Ko, JS | |
dc.contributor.author | Billings, SD | |
dc.contributor.author | Chen, S | |
dc.contributor.author | Abi Daoud, M | |
dc.contributor.author | Hewinson, J | |
dc.contributor.author | Louzada, S | |
dc.contributor.author | Harms, PW | |
dc.contributor.author | Cerretelli, G | |
dc.contributor.author | Robles-Espinoza, CD | |
dc.contributor.author | Patel, RM | |
dc.contributor.author | van der Weyden, L | |
dc.contributor.author | Bakal, C | |
dc.contributor.author | Hornick, JL | |
dc.contributor.author | Arends, MJ | |
dc.contributor.author | Brenn, T | |
dc.contributor.author | Adams, DJ | |
dc.date.accessioned | 2020-06-03T14:24:46Z | |
dc.date.issued | 2019-05-17 | |
dc.identifier.citation | Nature communications, 2019, 10 (1), pp. 2213 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3696 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-019-09979-0 | |
dc.description.abstract | Spiradenoma 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.format | Electronic | |
dc.format.extent | 2213 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Sweat Glands | |
dc.subject | Humans | |
dc.subject | Carcinoma, Adenoid Cystic | |
dc.subject | Sweat Gland Neoplasms | |
dc.subject | Protein Kinases | |
dc.subject | Cohort Studies | |
dc.subject | DNA Mutational Analysis | |
dc.subject | Mutation, Missense | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Tumor Suppressor Protein p53 | |
dc.subject | Protein Domains | |
dc.subject | Whole Exome Sequencing | |
dc.subject | Loss of Function Mutation | |
dc.subject | Deubiquitinating Enzyme CYLD | |
dc.subject | DNA (Cytosine-5-)-Methyltransferases | |
dc.title | ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-04-08 | |
rioxxterms.versionofrecord | 10.1038/s41467-019-09979-0 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-05-17 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Dynamical Cell Systems | |
dc.contributor.icrauthor | Butera, Francesca | |
dc.contributor.icrauthor | Bakal, Christopher | |