PMID- 25442074 OWN - NLM STAT- MEDLINE DCOM- 20150129 LR - 20151119 IS - 2210-7762 (Print) VI - 207 IP - 7-8 DP - 2014 Jul-Aug TI - Genomic microarray analysis on formalin-fixed paraffin-embedded material for uveal melanoma prognostication. PG - 306-15 LID - S2210-7762(14)00172-0 [pii] LID - 10.1016/j.cancergen.2014.08.005 [doi] AB - Cytogenetic alterations are strong outcome prognosticators in uveal melanoma (UVM). Monosomy 3 (-3) and MYC amplification at 8q24 are commonly tested by fluorescence in situ hybridization (FISH). Alternatively, microarray analysis provides whole genome data, detecting partial chromosome loss, loss of heterozygosity (LOH), or abnormalities unrepresented by FISH probes. Nonfixed frozen tissue is conventionally used for microarray analysis but may not always be available. We assessed the feasibility of genomic microarray analysis for high resolution interrogation of UVM using formalin-fixed paraffin-embedded tissue (FFPET) as an alternative to frozen tissue (FZT). Enucleations from 44 patients (clinical trial NCT00952939) yielded sufficient DNA from FFPET (n = 34) and/or frozen tissue (n = 41) for comparative genomic hybridization and select single nucleotide polymorphism analysis (CGH/SNP) on Roche-NimbleGen OncoChip arrays. CEP3 FISH analysis was performed on matched cytology ThinPrep material. CGH/SNP analysis was successful in 30 of 34 FFPET and 41 of 41 FZT samples. Of 27 paired FFPET/FZT samples, 26 (96.3%) were concordant for at least four of six major recurrent abnormalities (-3, +8q, -1p, +6p, -6q, -8p), and 25 of 27 (92.6%) were concordant for -3. Results of CGH/SNP were concordant with the CEP3 FISH results in 27 of 30 (90%) FFPET and 38 of 41 (92.6%) FZT cases; partial -3q was detected in two CEP3 FISH-negative cases and whole chromosome 3, 4, and 6 SNP-LOH in one case. CGH detection of -3, +8q, -8p on FFPET and FZT showed significant correlation with the clinical outcome measures (metastasis development, time to progression, survival). Results of the UVM genotyping by CGH/SNP on FFPET are highly concordant with those of the FZT analysis and with those of the CEP3 FISH analysis, and therefore CGH/SNP is a practical method for UVM prognostication. Genome-wide coverage provides additional data with potential relevance to UVM biology, diagnosis, and prognosis. CI - Copyright (c) 2014. Published by Elsevier Inc. FAU - Minca, Eugen C AU - Minca EC AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Tubbs, Raymond R AU - Tubbs RR AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Portier, Bryce P AU - Portier BP AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Wang, Zhen AU - Wang Z AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Lanigan, Christopher AU - Lanigan C AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Aronow, Mary E AU - Aronow ME AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Triozzi, Pierre L AU - Triozzi PL AD - Tausig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Singh, Arun AU - Singh A AD - Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Cook, James R AU - Cook JR AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Saunthararajah, Yogen AU - Saunthararajah Y AD - Tausig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Plesec, Thomas P AU - Plesec TP AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Schoenfield, Lynn AU - Schoenfield L AD - Departments of Molecular and Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Cawich, Victoria AU - Cawich V AD - Signature Genomics Laboratories, Perkin Elmer, Spokane, WA, USA. FAU - Sulpizio, Scott AU - Sulpizio S AD - Signature Genomics Laboratories, Perkin Elmer, Spokane, WA, USA. FAU - Schultz, Roger A AU - Schultz RA AD - Signature Genomics Laboratories, Perkin Elmer, Spokane, WA, USA. Electronic address: Roger.Schultz@PerkinElmer.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140829 PL - United States TA - Cancer Genet JT - Cancer genetics JID - 101539150 RN - 0 (Biomarkers, Tumor) RN - 0 (RNA, Messenger) RN - 1HG84L3525 (Formaldehyde) RN - Uveal melanoma SB - IM MH - Biomarkers, Tumor/*genetics MH - *Chromosome Aberrations MH - Comparative Genomic Hybridization MH - Feasibility Studies MH - Formaldehyde MH - *Gene Expression Profiling MH - Humans MH - In Situ Hybridization, Fluorescence MH - Melanoma/*genetics/pathology MH - Oligonucleotide Array Sequence Analysis MH - Paraffin Embedding MH - Polymorphism, Single Nucleotide/*genetics MH - Prognosis MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Uveal Neoplasms/*genetics/pathology OTO - NOTNLM OT - FFPE OT - Uveal melanoma OT - genomic OT - microarray OT - prognostic EDAT- 2014/12/03 06:00 MHDA- 2015/01/30 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/04/28 00:00 [received] PHST- 2014/07/07 00:00 [revised] PHST- 2014/08/21 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2015/01/30 06:00 [medline] AID - S2210-7762(14)00172-0 [pii] AID - 10.1016/j.cancergen.2014.08.005 [doi] PST - ppublish SO - Cancer Genet. 2014 Jul-Aug;207(7-8):306-15. doi: 10.1016/j.cancergen.2014.08.005. Epub 2014 Aug 29.