Porocarcinomas harbor recurrent HRAS-activating mutations and tumor suppressor inactivating mutations

Area of Science:

• Oncology
• Dermatopathology
• Cancer Genomics

Background:

• Porocarcinomas are rare eccrine carcinomas with high metastatic potential.
• The oncogenic drivers of porocarcinomas remain largely underexplored.
• Previous reports identified only one case with a PIK3CA-activating mutation.

Purpose of the Study:

• To analyze the genetic landscape of porocarcinomas.
• To identify potential oncogenic drivers and tumor suppressor inactivation events.
• To explore the role of specific mutations in porocarcinoma development and potential therapeutic targets.

Main Methods:

• Analysis of 5 porocarcinomas using next-generation sequencing (Oncomine Comprehensive Assay).
• Assessment of copy number changes and mutational events in 126 cancer-relevant genes.
• Targeted sequencing of benign eccrine poromas for comparison.

Main Results:

• An average of 3.3 nonsynonymous mutations per tumor were detected.
• Frequent tumor suppressor mutations included TP53 (80%) and RB1 (60%).
• Potential oncogenic drivers HRAS (40%) and EGFR (40%) were identified, with HRAS mutations also found in benign poromas.

Conclusions:

• HRAS and EGFR act as oncogenic drivers in a subset of porocarcinomas.
• TP53 and RB1 inactivation likely contribute to tumorigenesis.
• The diverse genetic drivers in porocarcinomas have implications for developing targeted therapies.