[480] 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 characteristics

Patient #	Age of 1st Dx/sex	Time to death/LF (years)	Status	Site of bx	stage at bx	RAS mutation
1	57M	1	DOD	skin	IIB	-
2	52M	12	DOD	LN	IVA2	-
3	16M	15	DOD	skin	IIB	+
4	60M	2	DOD	skin	IIB	-
5	23M	15	chronic	LN	IVA2	-
6	49M	14	DOD	skin	IIB*	-
7	74F	11	chronic	LN	IVA2	-
8	60M	2	DOD	skin	IVA1	-
9	68M	9	DOD	skin	IIB	-
10	82M	1	DOD	skin	IIB	-

Dx:diagnosis, LF:last follow up, bx: biopsy, DOD: dead of disease, *subsequently developed sezary syndrome


Conclusions: One of our cases was positive for a RAS G13D oncogene mutation similar to that previously described in a single case of stage IV MF. Features notable about our patient include young age at diagnosis, length of early stage disease, and lack of nodal or blood involvement. While it is difficult to draw definitive conclusions from a limited sample, we hypothesize that RAS mutations in MF may occur as a late event in the context of long-standing disease, and may serve as a marker of disease progression, rather than a cause.
Category: Dermatopathology

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 101, Tuesday Morning