Functional analysis of RPS27 mutations and expression in melanoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Next-generation sequencing (NGS) advances melanoma genomics.
• Identifying novel driver mutations in cutaneous melanoma is challenging due to high mutational background and limited whole-genome sequencing coverage.

Purpose of the Study:

• To investigate the somatic mutation portfolio in exonic and gene regulatory regions of human melanoma.
• To identify novel recurrent mutations and understand their functional impact on RPS27 expression and melanoma progression.

Main Methods:

• Targeted sequencing of tumors and matched germline DNA from 89 melanoma patients.
• In vitro assays, immunohistochemistry (IHC), data mining, and loss-of-function experiments.

Main Results:

• Identified recurrent mutations in the RPS27 promoter, decreasing RPS27 mRNA levels.
• Observed a bimodal RPS27 expression pattern in melanoma; low RPS27 correlated with worse prognosis.
• RPS27-high status increased proliferation and invasion; RPS27-low status conferred survival advantages and therapy resistance.
• Bimodal RPS27 expression and its association with worse outcomes were confirmed in 10 other cancer types.

Conclusions:

• RPS27 promoter mutations modulate gene expression, potentially serving as prognostic and predictive markers in melanoma.
• RPS27 expression patterns have significant clinical implications across multiple cancer types.