Journal Article

DKFZ-2021-01191

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies.

Denisova, E. (First author)DKFZ* ; Westphal, D. ; Surowy, H. M. ; Meier, F. ; Hutter, B.DKFZ* ; Reifenberger, J. ; Rütten, A. ; Schulz, A. ; Sergon, M. ; Ziemer, M. ; Brors, B.DKFZ* ; Betz, R. C. ; Redler, S.

2022
Nature Publ. Group New York, NY

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Please use a persistent id in citations: doi:10.1038/s41417-021-00347-z

Abstract: Malignant sweat gland tumours are rare, with the most common form being Eccrine porocarcinoma (EP). To investigate the mutational landscape of EP, we performed whole-exome sequencing (WES) on 14 formalin-fixed paraffin-embedded samples of matched primary EP and healthy surrounding tissue. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. Recurrent driving somatic alterations were detected in the EP candidate drivers TP53, FAT2, CACNA1S, and KMT2D. The analyses also identified copy number alterations and recurrent gains and losses in several chromosomal regions including that containing BRCA2, as well as deleterious alterations in multiple HRR components. In accordance with this reduced or even a complete loss of BRCA2 protein expression was detected in 50% of the investigated EP tumours. Our results implicate crucial oncogenic driver pathways and suggest that defective homologous double-strand break repair and the p53 pathway are involved in EP aetiology. Targeting of the p53 axis and PARP inhibition, and/or immunotherapy may represent promising treatment strategies.

Note: #EA:B330# / 2022 Jun;29(6):697-708

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Contributing Institute(s):

1. Angewandte Bioinformatik (B330)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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