Prognostic testing in uveal melanoma by transcriptomic profiling of fine needle biopsy specimens.
Many uveal melanoma patients die of metastasis despite ocular treatment. Transcriptomic profiling of enucleated tumors can identify patients at high metastatic risk. Because most uveal melanomas do not require enucleation, a biopsy would be required for this analysis. Here, we establish the feasibility of transcriptomic analysis of uveal melanomas from fine needle aspirates. Transcriptomic profiles were analyzed from postenucleation "mock" needle biopsies and matching tumors from eight enucleated eyes and from fine needle aspirates in 17 uveal melanomas before radiotherapy. Predictive accuracy was assessed using a weighted voting classifier optimized for probe set selection using a minimal redundancy/maximum relevance algorithm. Transcriptomic profiles from mock biopsies were highly similar to those from their matching tumor samples (P < 0.0001). Transcriptomic profiles from fine needle aspirates clustered into two classes with discriminating probe sets that overlapped significantly with those for our published classification (P < 0.00001). No loss of predictive accuracy was identified among eight needle aspirates obtained from a distant location. Thus, it is feasible to obtain RNA of adequate quality and quantity to perform transcriptomic analysis on uveal melanoma samples obtained by fine needle biopsy. This method can be applied to specimens obtained from distant geographic locations and can stratify uveal melanoma patients based on metastatic risk.
Onken
Michael D
MD
Box 8096, 660 South Euclid Ave., St. Louis, MO 63124, USA. harbour@wustl.edu
Worley
Lori A
LA
Dávila
Rosa M
RM
Char
Devron H
DH
Harbour
J William
JW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle / Q000379:methods*; D016000:Cluster Analysis; D005240:Feasibility Studies; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D008962:Models, Theoretical; D012107:Research Design; D014158:Transcription, Genetic; D014604:Uveal Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology