RAS Mutation Analysis of Transformed Mycosis Fungoides Identifies a KRAS G13D Mutation
Brian M Connolly, Cyrus Hedvat, Patricia L Myskowski, Steven M Horwitz, Melissa P Pulitzer. Memorial Sloan Kettering Cancer Center, New York
Background: Mycosis Fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), which, upon progression to tumors and/or large cell transformation (T-MF) may follow an aggressive course, with a mean survival <2 years. The molecular characterization of MF has been generally limited to cytogenetic and gene expression analyses. Mutation analysis of cancer-related genes in MF has rarely been performed. Recently, KRAS G13D and NRAS Q61K mutations in 2 cases each of stage IV CTCL were reported; one was in a lesion of MF. We investigated T-MF for RAS mutations using a Sequenom MassArray Platform.
Design: Ten FFPE tissue samples from patients with tumor (stage IIB: n=7) or nodal (stage IVA2; n=3) T-MF were retrieved from the pathology archive. Clinical and morphologic features were assessed; review of H&E sections confirmed abundant cellularity of samples. Genomic DNA was extracted from 5 micron thick tissue sections. Sequenom Mass Spectrometry Genotyping was used to assess for specific mutations in KRAS codons 12,13,61,117,146, and NRAS codons 12,13,61.
Results: One case showed a KRAS mutation in codon 13 (G13D). The specimen was from a skin tumor in a 28 year old patient with a 12 year history of MF, staged as IIB, who later died of disease. The remaining patients, 7 of whom died of disease, and including 3 with LN involvement (stage IVA2); and 2 with SS (stage IVA1), did not show mutations.
|Patient #||Age of 1st Dx/sex||Time to death/LF (years)||Status||Site of bx||stage at bx||RAS mutation|