Naslov
ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma

Autori
Rashid, Mamunur ; van der Horst, Michiel ; Mentzel, Thomas ; Butera, Francesca ; Ferreira, Ingrid ; Pance, Alena ; Rütten, Arno ; Luzar, Bostjan ; Marušić, Zlatko ; de Saint Aubain, Nicolas ; Ko, Jennifer S. ; Billings, Steven D. ; Chen, Sofia ; Abi Daoud, Marie ; Hewinson, James ; Louzada, Sandra ; Harms, Paul W. ; Cerretelli, Guia ; Robles-Espinoza, Carla Daniela ; Patel, Rajiv M. ; van der Weyden, Louise ; Bakal, Chris ; Hornick, Jason L. ; Arends, Mark J. ; Brenn, Thomas ; Adams, David J.

Izvornik
Nature Communications (2041-1723) 10 (2019), 1; 2213, 9

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
mutation ; spiradenoma ; spiradenocarcinoma

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA