TY - JOUR
T1 - Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma
AU - Onken, Michael D.
AU - Worley, Lori A.
AU - Person, Erica
AU - Char, Devron H.
AU - Bowcock, Anne M.
AU - Harbour, J. William
PY - 2007/5/15
Y1 - 2007/5/15
N2 - Purpose: Loss of chromosome 3 is strongly associated with metastasis in uveal melanoma and has been proposed as the basis for clinical prognostic testing. It is not known whether techniques that identify loss of heterozygosity for chromosome 3 predict metastasis more accurately than those that detect only numerical loss of chromosome 3 (monosomy 3). Experimental Design: Fifty-three uveal melanomas were analyzed by 28 single nucleotide polymorphisms (SNP) across chromosome 3. SNP was compared with fluorescence in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH) for metastasis prediction by sensitivity, specificity, and Kaplan-Meier survival analysts, using our validated gene expression-based classifier as a reference standard. Results: By Kaplan-Meier analysis, only the gene expression-based classifier (P = 0.001) and SNP-based detection of loss of heterozygosity for chromosome 3 (P = 0.04) were significantly associated with metastasis. Sensitivity and specificity were 95.2% and 80.8%, respectively, for SNP, 77.8% and 64.7%, respectively, for FISH, and 85.0% and 72.0%, respectively, for aCGH. Isodisomy 3 was identified by SNP but undetected by aCGH and FISH in three tumors. Conclusions: Prognostic tests based on SNP platforms, which detect both chromosomal homologues and their subregions, may be superior to techniques that only detect changes in chromosome number. These observations could have important implications for efforts to detect genetic alterations in cancer genomes with CGH-based approaches.
AB - Purpose: Loss of chromosome 3 is strongly associated with metastasis in uveal melanoma and has been proposed as the basis for clinical prognostic testing. It is not known whether techniques that identify loss of heterozygosity for chromosome 3 predict metastasis more accurately than those that detect only numerical loss of chromosome 3 (monosomy 3). Experimental Design: Fifty-three uveal melanomas were analyzed by 28 single nucleotide polymorphisms (SNP) across chromosome 3. SNP was compared with fluorescence in situ hybridization (FISH) and array-based comparative genomic hybridization (aCGH) for metastasis prediction by sensitivity, specificity, and Kaplan-Meier survival analysts, using our validated gene expression-based classifier as a reference standard. Results: By Kaplan-Meier analysis, only the gene expression-based classifier (P = 0.001) and SNP-based detection of loss of heterozygosity for chromosome 3 (P = 0.04) were significantly associated with metastasis. Sensitivity and specificity were 95.2% and 80.8%, respectively, for SNP, 77.8% and 64.7%, respectively, for FISH, and 85.0% and 72.0%, respectively, for aCGH. Isodisomy 3 was identified by SNP but undetected by aCGH and FISH in three tumors. Conclusions: Prognostic tests based on SNP platforms, which detect both chromosomal homologues and their subregions, may be superior to techniques that only detect changes in chromosome number. These observations could have important implications for efforts to detect genetic alterations in cancer genomes with CGH-based approaches.
UR - http://www.scopus.com/inward/record.url?scp=34249781123&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249781123&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-06-2383
DO - 10.1158/1078-0432.CCR-06-2383
M3 - Article
C2 - 17504992
AN - SCOPUS:34249781123
SN - 1078-0432
VL - 13
SP - 2923
EP - 2927
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -