116 Mosaic RASopathies associated with rhabdomyosarcoma

Abstract

Rationale: RAS genes are well-established oncogenes known to contribute to the development of cancer. Epidermal, sebaceous, and melanocytic nevi may be triggered by somatic mutations in HRAS, KRAS, and NRAS. The majority of these nevi are not associated with internal malignancies, however, a small subset have been associated with rhabdomyosarcoma (RMS). This calls into question the clinical utility of the anatomic location of the nevi for cancer risk stratification and management. Methods: A retrospective review showed 12 previously reported cases of RAS-driven nevi in conjunction with RMS. 3 additional unreported cases were collected from collaborators through the Pediatric Dermatology Research Alliance (PeDRA). Results: 15 patients with 16 primary RMS were included for analysis. 12/15 were previously reported.1-12 All had RAS-driven birthmarks: 5 patients with epidermal nevi, 4 with congenital melanocytic nevi, 4 with phacomatosis pigmentokeratotica, and 2 with speckled lentiginous nevi/agminated Spitz. Of the 16 RMS: 8 were genitourinary, 3 were pelvic/retroperitoneal, 4 were dermal, and 1 was abdominal. 5/15 tumor-birthmark pairs had genotyping results: 3 had HRAS mutations and 2 had KRAS mutations. Body surface area did not seem to be a contributing risk factor. However, all 15 cases had involvement of the nevus on the trunk. Relevance: Truncal location of mosaic RASopathies may be a risk factor for RMS. Further prospective studies are needed to solidify appropriate monitoring guidelines for patients at risk.