Gene expression profiling in aggressive digital papillary adenocarcinoma sheds light on the architecture of a rare sweat gland carcinoma.


Journal

The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041

Informations de publication

Date de publication:
05 2019
Historique:
accepted: 16 11 2018
pubmed: 26 11 2018
medline: 1 8 2020
entrez: 26 11 2018
Statut: ppublish

Résumé

Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA. To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue. Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction. Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0·001). The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas.

Sections du résumé

BACKGROUND
Sweat gland carcinomas are rare cutaneous adnexal malignancies. Aggressive digital papillary adenocarcinoma (ADPA) represents a very rare subentity, thought to arise almost exclusively from the sweat glands of the fingers and toes. The aetiology of sweat gland carcinomas and ADPA is largely unknown. ADPAs are most likely driven by somatic mutations. However, somatic mutation patterns are largely unexplored, creating barriers to the development of effective therapeutic approaches to the treatment of ADPA.
OBJECTIVES
To investigate the transcriptome profile of ADPA using a sample of eight formalin-fixed, paraffin-embedded tissue samples of ADPA and healthy control tissue.
METHODS
Transcriptome profiling was performed using the Affymetrix PrimeView Human Gene Expression Microarray and findings were validated via reverse transcription of RNA and real-time quantitative polymerase chain reaction.
RESULTS
Transcriptome analyses showed increased tumour expression of 2266 genes, with significant involvement of cell cycle, ribosomal and crucial cancer pathways. Our results point to tumour overexpression of FGFR2 (P = 0·001).
CONCLUSIONS
The results indicate the involvement of crucial oncogenic driver pathways, highlighting cell cycle and ribosomal pathways in the aetiology of ADPA. Suggested tumour overexpression of FGFR2 raises the hope that targeting the fibroblast growth factor (FGF)/FGF receptor axis might be a promising treatment for ADPA and probably for the overall group of sweat gland carcinomas.

Identifiants

pubmed: 30472730
doi: 10.1111/bjd.17446
doi:

Substances chimiques

FGFR2 protein, human EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 2 EC 2.7.10.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1150-1160

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2018 British Association of Dermatologists.

Auteurs

H M Surowy (HM)

Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, Düsseldorf, Germany.

A K Giesen (AK)

Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, Düsseldorf, Germany.

J Otte (J)

Institute for Stem Cell Research and Regenerative Medicine, Düsseldorf, Germany.

R Büttner (R)

Pathology, Institute for Pathology, University Hospital Cologne, Cologne, Germany.

D Falkenstein (D)

Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, Düsseldorf, Germany.

H Friedl (H)

Klinikum Darmstadt, Department of Dermatology, Darmstadt, Germany.

F Meier (F)

Department of Dermatology, Carl Gustav Carus Medical Center, TU Dresden, Dresden, Germany.
National Center for Tumour Diseases (NCT), Partner Site Dresden, Dresden, Germany.

P Petzsch (P)

Biological and Medical Research Center (BMFZ), Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

T Wachtmeister (T)

Biological and Medical Research Center (BMFZ), Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

D Westphal (D)

Department of Dermatology, Carl Gustav Carus Medical Center, TU Dresden, Dresden, Germany.
National Center for Tumour Diseases (NCT), Partner Site Dresden, Dresden, Germany.

D Wieczorek (D)

Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, Düsseldorf, Germany.

W Wruck (W)

Institute for Stem Cell Research and Regenerative Medicine, Düsseldorf, Germany.

J Adjaye (J)

Institute for Stem Cell Research and Regenerative Medicine, Düsseldorf, Germany.

A Rütten (A)

Dermatopathology, Bodensee, Siemensstrasse 6/1, 88048, Friedrichshafen, Germany.

S Redler (S)

Heinrich-Heine-University, Medical Faculty, Institute of Human Genetics, Düsseldorf, Germany.

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Classifications MeSH