Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma

Michael D. Onken, Lori A. Worley, Erica Person, Devron H. Char, Anne M. Bowcock, J. William Harbour

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2923-2927
Number of pages5
JournalClinical Cancer Research
Volume13
Issue number10
DOIs
StatePublished - May 15 2007
Externally publishedYes

Fingerprint

Monosomy
Chromosomes, Human, Pair 3
Loss of Heterozygosity
Single Nucleotide Polymorphism
Neoplasm Metastasis
Comparative Genomic Hybridization
Fluorescence In Situ Hybridization
Gene Expression
Sensitivity and Specificity
Kaplan-Meier Estimate
In Situ Hybridization
Uveal melanoma
Neoplasms
Research Design
Chromosomes
Genome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma. / Onken, Michael D.; Worley, Lori A.; Person, Erica; Char, Devron H.; Bowcock, Anne M.; William Harbour, J.

In: Clinical Cancer Research, Vol. 13, No. 10, 15.05.2007, p. 2923-2927.

Research output: Contribution to journalArticle

Onken, Michael D. ; Worley, Lori A. ; Person, Erica ; Char, Devron H. ; Bowcock, Anne M. ; William Harbour, J. / Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 10. pp. 2923-2927.
@article{84d807af2a85449f8f32ea17e151b518,
title = "Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma",
abstract = "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.",
author = "Onken, {Michael D.} and Worley, {Lori A.} and Erica Person and Char, {Devron H.} and Bowcock, {Anne M.} and {William Harbour}, J.",
year = "2007",
month = "5",
day = "15",
doi = "10.1158/1078-0432.CCR-06-2383",
language = "English",
volume = "13",
pages = "2923--2927",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

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 - William Harbour, J.

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

VL - 13

SP - 2923

EP - 2927

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 10

ER -