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Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
c-Kit expression and mutations in phyllodes tumors of the breast
Prithviraj Bose1, S Terence Dunn, Jian Yang
1Department of Medicine, Section of Hematology-Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126, USA. pbose@mcvh-vcu.edu
Background:
Phyllodes tumors (PTs) represent uncommon fibroepithelial lesions of the breast that express c-Kit and platelet-derived growth factor receptor-alpha, similar to gastrointestinal stromal tumors (GISTs). 'Activating' mutations in these genes underlie responsiveness of GISTs to imatinib. Standard treatment for breast PTs is wide local excision, with no role for targeted therapies.
Patients And Methods:
c-Kit (CD117) expression was investigated by immunohistochemistry in 17 cases of breast PTs. Fourteen of these cases were also subjected to KIT mutation analysis by dideoxynucleotide sequencing.
Results:
Five out of 17 (29%) tumors showed weak stromal staining for CD117. No previously described 'activating' mutations were found in exons 9, 11, 13, or 17 of the KIT gene. A silent germline point mutation was found in exon 17 of one case.
Conclusion:
These data do not suggest a pathogenetic role for KIT in breast PTs. Inhibition of c-Kit signaling is unlikely to be helpful in this condition.
Insights
Phyllodes tumors (PTs) of the breast do not show activating KIT mutations. Therefore, targeted therapies like imatinib, effective for similar mutations in gastrointestinal stromal tumors (GISTs), are unlikely to benefit patients with PTs.
Area of Science:
- Oncology
- Molecular Pathology
- Breast Cancer Research
Background:
- Phyllodes tumors (PTs) are rare fibroepithelial breast lesions.
- PTs share molecular similarities, including c-Kit expression, with gastrointestinal stromal tumors (GISTs).
- GISTs with specific KIT mutations respond to imatinib therapy.
Purpose of the Study:
- To investigate the role of KIT mutations in the pathogenesis of breast PTs.
- To determine if breast PTs harbor activating mutations in the KIT gene.
- To assess the potential for targeted therapy in breast PTs.
Main Methods:
- Immunohistochemistry was used to evaluate c-Kit (CD117) expression in 17 breast PT cases.
- KIT gene mutation analysis (exons 9, 11, 13, 17) was performed on 14 PT samples using dideoxynucleotide sequencing.
Main Results:
- c-Kit (CD117) expression was detected in the stroma of 29% (5/17) of breast PTs.
- No previously identified activating mutations in the KIT gene were found in any of the analyzed PTs.
- A single silent germline mutation in KIT exon 17 was observed in one case.
Conclusions:
- The study findings do not support a role for KIT gene mutations in the development of breast PTs.
- Targeted inhibition of c-Kit signaling is unlikely to be an effective treatment strategy for phyllodes tumors of the breast.
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