Loss of ZNF750 in ocular and cutaneous sebaceous carcinoma.
ZNF750
sebaceous adenoma
sebaceous carcinoma
Journal
Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
08
01
2019
revised:
24
05
2019
accepted:
28
05
2019
pubmed:
31
5
2019
medline:
7
2
2020
entrez:
1
6
2019
Statut:
ppublish
Résumé
Sebaceous carcinoma (SeC) is an uncommon malignancy arising from sebaceous glands of the conjunctiva and skin. Recurrent mutations in the ZNF750 were recently identified in ocular SeC. We assessed whether ZNF750 loss is a specific feature of ocular SeC or a general feature of sebaceous tumors. Immunostaining for ZNF750 expression was performed in 54 benign and malignant sebocytic proliferations. Staining for ZNF750 was scored on a three-tier scale: positive (>75%), partially positive (5%-74%), and negative (<5%). ZNF750 expression was negative in 4/11 ocular SeC, and partially positive in 4/11 ocular SeC and 6/13 cutaneous SeC. No extraocular tumors were negative. No loss was found in sebaceous adenoma or sebaceous hyperplasia. In nine previously sequenced ocular SeCs, two lacked detectable somatic mutations in ZNF750, but showed complete loss of staining, indicating non-mutational inactivation of ZNF750. We show complete loss of the ZNF750 epidermal differentiation regulator in about half of ocular SeC, highlighting the most common genetic defect in this cancer type. Loss of ZNF750 expression is seen even in tumors without truncating mutations and reduced in many of the remaining ocular and cutaneous SeC. In contrast, no ZNF750 loss was detected in benign sebaceous proliferations.
Sections du résumé
BACKGROUND
BACKGROUND
Sebaceous carcinoma (SeC) is an uncommon malignancy arising from sebaceous glands of the conjunctiva and skin. Recurrent mutations in the ZNF750 were recently identified in ocular SeC. We assessed whether ZNF750 loss is a specific feature of ocular SeC or a general feature of sebaceous tumors.
METHODS
METHODS
Immunostaining for ZNF750 expression was performed in 54 benign and malignant sebocytic proliferations. Staining for ZNF750 was scored on a three-tier scale: positive (>75%), partially positive (5%-74%), and negative (<5%).
RESULTS
RESULTS
ZNF750 expression was negative in 4/11 ocular SeC, and partially positive in 4/11 ocular SeC and 6/13 cutaneous SeC. No extraocular tumors were negative. No loss was found in sebaceous adenoma or sebaceous hyperplasia. In nine previously sequenced ocular SeCs, two lacked detectable somatic mutations in ZNF750, but showed complete loss of staining, indicating non-mutational inactivation of ZNF750.
CONCLUSION
CONCLUSIONS
We show complete loss of the ZNF750 epidermal differentiation regulator in about half of ocular SeC, highlighting the most common genetic defect in this cancer type. Loss of ZNF750 expression is seen even in tumors without truncating mutations and reduced in many of the remaining ocular and cutaneous SeC. In contrast, no ZNF750 loss was detected in benign sebaceous proliferations.
Identifiants
pubmed: 31148199
doi: 10.1111/cup.13516
pmc: PMC6744339
mid: NIHMS1035267
doi:
Substances chimiques
Neoplasm Proteins
0
Transcription Factors
0
Tumor Suppressor Proteins
0
ZNF750 protein, human
0
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
736-741Subventions
Organisme : UCSF Physician-Scientist Scholar Program
Organisme : UCSF Department of Dermatology
Organisme : NIH HHS
ID : DP5 OD021403
Pays : United States
Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Nat Genet. 2006 Jul;38(7):749-51
pubmed: 16751772
Cancer. 2009 Jan 1;115(1):158-65
pubmed: 18988294
Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17761-6
pubmed: 22006338
Dev Cell. 2012 Mar 13;22(3):669-77
pubmed: 22364861
J Am Acad Dermatol. 2013 Mar;68(3):509-10
pubmed: 23394915
Nat Genet. 2014 May;46(5):467-73
pubmed: 24686850
Cell Cycle. 2014;13(13):2013-4
pubmed: 24901941
Genes Dev. 2014 Sep 15;28(18):2013-26
pubmed: 25228645
Dermatol Surg. 2015 Jan;41(1):1-15
pubmed: 25521100
Gastroenterology. 2016 May;150(5):1171-1182
pubmed: 26873401
J Pathol. 2016 Sep;240(1):84-95
pubmed: 27287813
Oncogene. 2017 Apr 20;36(16):2243-2254
pubmed: 27819679
Oncology. 2018;94(3):142-148
pubmed: 29216641
Oncotarget. 2017 Dec 9;9(1):566-575
pubmed: 29416636
Nat Commun. 2018 May 14;9(1):1894
pubmed: 29760388
Clin Cancer Res. 2019 Feb 15;25(4):1280-1290
pubmed: 30420449