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

Autor: Jon M. Davison, Christin M. Sciulli, Maureen A. Lyons-Weiler, James D. Luketich, Melissa K. Yee, George K. Michalopoulos, Lori A. Kelly, William A. LaFramboise, Katie S. Nason, J. Michael Krill-Burger
Rok vydání: 2013
Předmět:
Oncology
Male
Pathology
Esophageal Neoplasms
Receptor
ErbB-2
Gene Dosage
Aneuploidy
lcsh:Medicine
Kaplan-Meier Estimate
medicine.disease_cause
Chromosomal Disorders
0302 clinical medicine
FHIT
CDKN2A
Gastrointestinal Cancers
Basic Cancer Research
lcsh:Science
In Situ Hybridization
Fluorescence
Chromosome 7 (human)
0303 health sciences
Multidisciplinary
Cancer Risk Factors
Statistics
Genomics
Middle Aged
Proto-Oncogene Proteins c-met
Genome Scans
3. Good health
ErbB Receptors
030220 oncology & carcinogenesis
Adenocarcinoma
Medicine
Female
KRAS
Molecular Pathology
Research Article
WWOX
medicine.medical_specialty
Prognostic variable
DNA Copy Number Variations
Esophageal Cancer
Genetic Causes of Cancer
Gastroenterology and Hepatology
Biology
Biostatistics
Disease-Free Survival
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Esophagus
Genome Analysis Tools
Diagnostic Medicine
Internal medicine
Gastrointestinal Tumors
medicine
Genetics
Humans
Genetic Association Studies
030304 developmental biology
Aged
Clinical Genetics
lcsh:R
Cancers and Neoplasms
Human Genetics
medicine.disease
Multivariate Analysis
lcsh:Q
Neoplasm Recurrence
Local
Mathematics
Biomarkers
General Pathology
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 1, p e79079 (2014)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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