DNA copy number alterations correlate with survival of esophageal adenocarcinoma patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-09-26

AUTHORS

Giulia Pasello, Simona Agata, Laura Bonaldi, Alberto Corradin, Marco Montagna, Rita Zamarchi, Anna Parenti, Matteo Cagol, Giovanni Zaninotto, Alberto Ruol, Ermanno Ancona, Alberto Amadori, Daniela Saggioro

ABSTRACT

Despite recent advances in surgical and multidisciplinary treatment, prognosis for patients with esophageal adenocarcinoma remains poor, and the low prognostic significance of pTNM staging suggests that additional parameters are needed. To identify genomic abnormalities characteristic of esophageal adenocarcinoma, a panel of 33 samples obtained at surgery from previously untreated patients were analyzed by muliplex ligation-dependent probe amplification technique. We detected frequent gains of 6p, 8q, 13q, 17q, 20q, and losses of 4q, 5q, 15q, and 18q. When DNA copy number changes were correlated to clinicopathological features of patients no association was found between the number of chromosomal aberrations and gender, age, tumor grade or pTNM staging. However, interestingly, a significant correlation between patient survival and total number of chromosomal aberrations was found when esophageal adenocarcinoma cases were stratified according to the median of survival (20 months) (P=0.002) or the median of aberrations (12 aberrations) (P=0.014). Evaluation of the distribution of gains and losses at the level of single chromosomes indicated that gains on chromosomes 5, 6, 8, 11, 20 and losses on chromosomes 1, 3, 5, 11, and 18 were significantly different in the two survival groups. Furthermore, when single gene imbalances were analyzed in further details, we found that besides alterations that involve genes shared by both survival groups, a few genes (KIAA0170, EMS1, ABCC4, F3, and MIF) were altered only in samples from patients with poor survival. Thus, we established a good correlation between the total number of chromosomal alterations and survival, suggesting that the estimation of total imbalances might represent an additional indicator of disease outcome. In addition, the finding of alterations specific for the more aggressive esophageal adenocarcinoma subset might represent promising biomarkers to increase the accuracy of clinical outcome prediction. More... »

PAGES

58-65

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/modpathol.2008.150

DOI

http://dx.doi.org/10.1038/modpathol.2008.150

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18820669


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25 schema:description Despite recent advances in surgical and multidisciplinary treatment, prognosis for patients with esophageal adenocarcinoma remains poor, and the low prognostic significance of pTNM staging suggests that additional parameters are needed. To identify genomic abnormalities characteristic of esophageal adenocarcinoma, a panel of 33 samples obtained at surgery from previously untreated patients were analyzed by muliplex ligation-dependent probe amplification technique. We detected frequent gains of 6p, 8q, 13q, 17q, 20q, and losses of 4q, 5q, 15q, and 18q. When DNA copy number changes were correlated to clinicopathological features of patients no association was found between the number of chromosomal aberrations and gender, age, tumor grade or pTNM staging. However, interestingly, a significant correlation between patient survival and total number of chromosomal aberrations was found when esophageal adenocarcinoma cases were stratified according to the median of survival (20 months) (P=0.002) or the median of aberrations (12 aberrations) (P=0.014). Evaluation of the distribution of gains and losses at the level of single chromosomes indicated that gains on chromosomes 5, 6, 8, 11, 20 and losses on chromosomes 1, 3, 5, 11, and 18 were significantly different in the two survival groups. Furthermore, when single gene imbalances were analyzed in further details, we found that besides alterations that involve genes shared by both survival groups, a few genes (KIAA0170, EMS1, ABCC4, F3, and MIF) were altered only in samples from patients with poor survival. Thus, we established a good correlation between the total number of chromosomal alterations and survival, suggesting that the estimation of total imbalances might represent an additional indicator of disease outcome. In addition, the finding of alterations specific for the more aggressive esophageal adenocarcinoma subset might represent promising biomarkers to increase the accuracy of clinical outcome prediction.
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32 schema:keywords DNA copy number alterations correlate
33 DNA copy number changes
34 aberrations
35 abnormalities
36 accuracy
37 addition
38 additional indicators
39 additional parameters
40 adenocarcinoma
41 adenocarcinoma cases
42 adenocarcinoma patients
43 adenocarcinoma subset
44 advances
45 age
46 aggressive esophageal adenocarcinoma subset
47 alterations
48 alterations correlate
49 amplification techniques
50 association
51 biomarkers
52 cases
53 changes
54 chromosomal aberrations
55 chromosomal alterations
56 chromosome 1
57 chromosome 5
58 chromosomes
59 clinical outcome prediction
60 clinicopathological features
61 copy number alterations correlate
62 copy number changes
63 correlates
64 correlation
65 detail
66 disease outcome
67 distribution
68 distribution of gains
69 esophageal adenocarcinoma
70 esophageal adenocarcinoma cases
71 esophageal adenocarcinoma patients
72 esophageal adenocarcinoma subset
73 estimation
74 evaluation
75 features
76 findings
77 findings of alterations
78 frequent gains
79 further details
80 gain
81 gender
82 gene imbalance
83 genes
84 genomic abnormalities
85 good correlation
86 grade
87 group
88 imbalance
89 indicators
90 levels
91 ligation-dependent probe amplification technique
92 loss
93 low prognostic significance
94 median
95 median of aberrations
96 median of survival
97 muliplex ligation-dependent probe amplification technique
98 multidisciplinary treatment
99 number
100 number alterations correlate
101 number changes
102 outcome prediction
103 outcomes
104 pTNM staging
105 panel
106 parameters
107 patient survival
108 patients
109 poor survival
110 prediction
111 probe amplification technique
112 prognosis
113 prognostic significance
114 promising biomarker
115 recent advances
116 samples
117 significance
118 significant correlation
119 single chromosome
120 single gene imbalances
121 staging
122 subset
123 surgery
124 survival
125 survival group
126 technique
127 total imbalance
128 total number
129 treatment
130 tumor grade
131 untreated patients
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