Abstract
BackgroundEsophageal adenocarcinoma (EA) is among the leading causes of cancer mortality, especially in developed countries. A high level of somatic copy number alterations (CNAs) accumulates over the decades in the progression from Barrett’s esophagus, the precursor lesion, to EA. Accurate identification of somatic CNAs is essential to understand cancer development. Many studies have been conducted for the detection of CNA in EA using microarrays. Next-generation sequencing (NGS) technologies are believed to have advantages in sensitivity and accuracy to detect CNA, yet no NGS-based CNA detection in EA has been reported.ResultsIn this study, we analyzed whole-exome (WES) and whole-genome sequencing (WGS) data for detecting CNA from a published large-scale genomic study of EA. Two specific comparisons were conducted. First, the recurrent CNAs based on WGS and WES data from 145 EA samples were compared to those found in five previous microarray-based studies. We found that the majority of the previously identified regions were also detected in this study. Interestingly, some novel amplifications and deletions were discovered using the NGS data. In particular, SKI and PRKCZ detected in a deletion region are involved in transforming growth factor-β pathway, suggesting the potential utility of novel biomarkers for EA. Second, we compared CNAs detected in WGS and WES data from the same 15 EA samples. No large-scale CNA was identified statistically more frequently by WES or WGS, while more focal-scale CNAs were detected by WGS than by WES.ConclusionsOur results suggest that NGS can replace microarrays to detect CNA in EA. WGS is superior to WES in that it can offer finer resolution for the detection, though if the interest is on recurrent CNAs, WES can be preferable to WGS for its cost-effectiveness.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-015-0044-0) contains supplementary material, which is available to authorized users.
Highlights
Esophageal adenocarcinoma (EA) is among the leading causes of cancer mortality, especially in developed countries
We further investigated if the falsepositive detection rates of small copy number alterations (CNAs) (
We found that the majority of the regions detected by microarrays overlapped the regions identified by Next-generation sequencing (NGS) and vise versa
Summary
Esophageal adenocarcinoma (EA) is among the leading causes of cancer mortality, especially in developed countries. A high level of somatic copy number alterations (CNAs) accumulates over the decades in the progression from Barrett’s esophagus, the precursor lesion, to EA. Accurate identification of somatic CNAs is essential to understand cancer development. Cancer arises from gradual accumulation of somatic genomic instability and alterations, which eventually lead to carcinogenesis and cancer progression [1, 2]. Detection of CNA is important to understand cancer development and identify key driver events [3, 4]. Microarray technologies have been widely used in CNA detection [5,6,7], including array comparative. Next-generation sequencing (NGS) technologies offer single-nucleotide resolution and absolute counts of read numbers and can provide more sensitive and accurate CNA results. With its ever-decreasing cost, NGS will replace microarrays in copy number analyses [10]
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