Esophageal Adenocarcinoma Methods and Protocols

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more sensitive tumor response marker in comparison to the changes

in morphological tumor phenotype. For example, patients whom

responded to neoadjuvant cisplatin-based chemotherapy and were

tested to have lower EGFR copy number had a significantly better

disease-free survival than nonresponders. In addition, nonresponder

patients were more often associated with amplified EGFR copy.

Thus, EGFR copy number may act as an independent adverse prog-

nostic factor for patients with esophageal adenocarcinoma on neo-

adjuvant cisplatin-based chemotherapy [ 43 ].

Identification of copy-number changes such as the amplifica-

tion of mitochondria DNA (mtDNA) in the peripheral blood leu-

kocytes [ 44 ] or tissue [ 45 ] was associated with increased

susceptibility to esophageal adenocarcinoma. Meanwhile, murine

double minute-2 (MDM2) can be used as a pre-screening tool

before following up with fluorescence in situ hybridisation (FISH)

for identification of esophageal adenocarcinoma [ 29 ].

Somatic copy-number alterations can also be used to predict

outcomes of esophageal adenocarcinoma. For example, lower level

of HER-2 was correlated to better outcome [ 46 ] while a relatively

lower increase in ZNF217 copy number was associated with poorer

prognosis and a higher copy number was correlated with improved

outcome [ 46 ]. Combined amplification of cyclin-dependent kinase

4 and 6 (CDK4 and CDK6) functioned as a better predictor of

survival outcome than individually [ 47 ].

Specific somatic copy-number alterations analysis has also been

a major help in considering target therapy options for esophageal

adenocarcinoma. For example, 15% of the patients with esophageal

adenocarcinoma that are found to have an overamplification of

Table 1
(continued)

Amplification/

Deletion Gene Ref.

Platelet derived growth factor subunit B (PDGFB) [ 13 ]

Protein Tyrosine Phosphatase, Receptor Type D

(PTPRD)

[ 19 ]

Phosphodiesterase 4D (PDE4D) [ 15 ]

Runt-related transcription factor 1 (RUNX1) [ 17 , 36 ]

SMAD Family Member 4 (SMAD4) [ 15 , 17 , 19 , 36 ]

Selenium-binding protein 1 (SELENBP1) [ 41 ]

The Ras-association domain family member 1 (RASSFI) [ 13 ]

WW domain containing oxidoreductase (WWOX) [ 15 , 17 ]

3-Hydroxyacyl-CoA dehydratase 4 (HACD4, PTPLAD2) [ 11 ]

DNA Copy-Number in Esophageal Adenocarcinoma