Journal article
Specific analysis of KIT and PDGFR‐alpha expression and mutational status in Merkel cell carcinoma
Journal of cutaneous pathology, Vol.40(7), pp.623-630
07/2013
DOI: 10.1111/cup.12160
PMID: 23621836
Abstract
Background
The purpose of this study was to explore the immunohistochemical and mutational status of the tyrosine kinases KIT and platelet derived growth receptor‐alpha (PDGFRA) in Merkel cell carcinoma (MCC). Specifically, we examined the mutated exons in gastrointestinal stromal cell tumors that may confer a treatment response to imatinib mesylate.
Methods
We evaluated KIT and PDGFRA immunostaining in 23 examples of MCC utilizing laser capture microdissection to obtain pure samples of tumor genomic DNA from 18 of 23 examples of MCC. PCR amplification and sequencing of KIT exons 9, 11, 13 and 17, and PDGFRA exons 10, 12, 14 and 18 for mutations was performed.
Results
Fifteen of 23 tumors (65%) demonstrated CD117 expression and 22 of 23 tumors (95%) demonstrated PDGFRA expression. A single heterozygous KIT exon 11 base change resulting in an E583K mutation was discovered in 12 of 18 (66%) examples of MCC. In addition, a single nucleotide polymorphism was detected in eight of 18 tumors (44%) in exon 18 of PDGFRA (codon 824; GTC > GTT).
Conclusions
We discovered a novel somatic KIT exon 11 E583K mutation in 66% of tumors. This mutation has been previously described in a human with piebaldism and appears to represent an inactivating mutation. Therefore, despite expression of CD117 and PDGFRA, the absence of activating mutations in these tyrosine kinases makes KIT and PDGFRA unlikely candidates of MCC oncogenesis.
Details
- Title: Subtitle
- Specific analysis of KIT and PDGFR‐alpha expression and mutational status in Merkel cell carcinoma
- Creators
- Brian L Swick - Iowa City Veterans Affairs Medical CenterRupasree Srikantha - University of IowaKelly N Messingham - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of cutaneous pathology, Vol.40(7), pp.623-630
- Publisher
- Blackwell Publishing Ltd; Oxford, UK
- DOI
- 10.1111/cup.12160
- PMID
- 23621836
- ISSN
- 0303-6987
- eISSN
- 1600-0560
- Number of pages
- 8
- Language
- English
- Date published
- 07/2013
- Academic Unit
- Dermatology; Pathology
- Record Identifier
- 9984025338402771
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