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Published on: July 25, 2020
Targeted Sequencing Revealed Distinct Mutational Profiles of Ocular and Extraocular Sebaceous Carcinomas
Hee Young Na1,2, Jeong Hwan Park1,3, Sun Ah Shin1,4
1Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Korea.
Abstract:
The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.
Insights
This study investigated genetic mutations in sebaceous carcinoma (SeC) in Korean patients. Key mutations in TP53, PIK3CA, and NOTCH1 were identified, with RUNX1 and ATM mutations linked to metastasis.
Area of Science:
- Oncology
- Genetics
- Dermatology
Background:
- Sebaceous carcinoma (SeC) exhibits indolent behavior but can invade locally or metastasize.
- Understanding the genetic landscape of SeC is crucial for developing effective systemic therapies.
- Korean patients with SeC were studied to explore genetic alterations.
Purpose of the Study:
- To investigate major genetic alterations in ocular (SeC-Os) and extraocular (SeC-EOs) sebaceous carcinoma in Korean patients.
- To identify potential molecular markers associated with SeC progression and patient outcomes.
- To explore the potential for targeted therapies based on identified genetic mutations.
Main Methods:
- Targeted next-generation sequencing of 171 cancer-related genes was performed on 29 SeC samples (20 SeC-Os, 9 SeC-EOs).
- Genetic alterations were analyzed in relation to clinical data, including metastasis and progression-free survival.
Main Results:
- TP53 and PIK3CA mutations were frequent in both SeC subtypes, with a slight predominance in SeC-Os.
- NOTCH1 mutations were more common in SeC-EOs.
- RUNX1 and ATM mutations correlated with distant metastasis development.
- MSH6 and BRCA1 alterations were associated with poorer progression-free survival (p < 0.05).
Conclusions:
- Distinct genetic alterations characterize SeC-Os and SeC-EOs.
- Specific gene mutations (RUNX1, ATM, MSH6, BRCA1) serve as important prognostic markers.
- The presence of actionable mutations (EGFR, ERBB2, mismatch repair genes) suggests potential for targeted clinical trials in advanced SeC cases.
