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The degree of segmental aneuploidy measured by total copy number abnormalities predicts survival and recurrence in superficial gastroesophageal adenocarcinoma

Davison, JM and Yee, M and Krill-Burger, JM and Lyons-Weiler, MA and Kelly, LA and Sciulli, CM and Nason, KS and Luketich, JD and Michalopoulos, GK and LaFramboise, WA (2014) The degree of segmental aneuploidy measured by total copy number abnormalities predicts survival and recurrence in superficial gastroesophageal adenocarcinoma. PLoS ONE, 9 (1).

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Abstract

Background: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC. Methods: We quantified copy number changes in 41 superficial EAC using Affymetrix SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and calculated the total copy number abnormality (CNA) count for each tumor as a measure of aneuploidy. We correlated CNA count with overall survival and time to first recurrence in univariate and multivariate analyses. Results: Recurrent segmental gains and losses involved multiple genes, including: HER2, EGFR, MET, CDK6, KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent losses). There was a 40-fold variation in CNA count across all cases. Tumors with the lowest and highest quartile CNA count had significantly better overall survival (p = 0.032) and time to first recurrence (p = 0.010) compared to those with intermediate CNA counts. These associations persisted when controlling for other prognostic variables. Significance: SNP arrays facilitate the assessment of recurrent chromosomal gain and loss and allow high resolution, quantitative assessment of segmental aneuploidy (total CNA count). The non-monotonic association of segmental aneuploidy with survival has been described in other tumors. The degree of aneuploidy is a promising prognostic biomarker in a potentially curable form of EAC. © 2014 Davison et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Davison, JMjmd91@pitt.eduJMD91
Yee, M
Krill-Burger, JM
Lyons-Weiler, MA
Kelly, LA
Sciulli, CMcms85@pitt.eduCMS85
Nason, KSksn7@pitt.eduKSN7
Luketich, JDluketich@pitt.eduLUKETICH
Michalopoulos, GKmichal@pitt.eduMICHAL
LaFramboise, WAwal9@pitt.eduWAL90000-0002-6024-810X
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorPack, SvetlanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 16 January 2014
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 9
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0079079
Schools and Programs: School of Medicine > Cardiothoracic Surgery
School of Medicine > Medicine
School of Medicine > Pathology
Refereed: Yes
Date Deposited: 19 Jun 2014 17:07
Last Modified: 04 Feb 2019 18:55
URI: http://d-scholarship.pitt.edu/id/eprint/21873

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