The authors present the genomic characterization of Esophageal Squamous Cell Carcinoma (ESCC) tumors in different stages, aiming to detect novel oncogenic mechanisms using NGS based whole-genome-sequencing or whole exome-sequencing of 51 stage I and 53 stage III ESCC patients. The authors report recurrent somatic amplifications at 8q enriched in stage I tumors and the deletions of 4p-q, 5q in tumors of stage III.
Previous whole genome copy number profiling studies, using SNP arrays (Brow J, et.al. 2011) on cell lines, identified amplification on 8q24.21 (C-MYC, FAM84B) associated with ESCC. Additionally, FAM84B gene has been previously associated with prostate cancer (Wang NN, et. al. 2013; Du M, et. al. 2014). The results present by the authors seems to be concordant with previous studies, increasing the confidence on the conclusions reached.

Minor Essential Revisions:

1. The author should highlight in the manuscript, that results presented are the genomic characterization of Han Chinese population only, no other ethnic groups where included in the study.

2. It is unclear whether basic raw data Quality Control was performed on the sequence data, if it was, the authors should describe the process/tool used.

3. It is unclear whether reads pre-processing steps (like adaptor removal) were applied to the sequence data (tools like SeqPrep, Cutadapt) if it was, the authors should describe the process/tools used.

4. The authors describe that in-house pipeline ‘CSAP’ was used to call somatic mutations, the authors should briefly describe the CSAP pipeline or provide a valid reference.

5. The authors describe that Somatic Mutation detection was performed using VarScan2. Comparative analysis of the performance of similar tools (SomaticSniper, Virmid, Strelka) shows only a small percentage of overlap or agreement between tools, the authors should describe why they choose VarScan2.

6. The authors describe that ‘High confident SNVs were annotated with ANNOVAR and used in follow-up analysis’, how the confidence/high confidence was defined? Similarly, it is important to know how high confident indels were defined.

7. The authors state that performed SegSeq to infer somatic copy number variation, please provide a reference to SeqSeq or briefly describe the method used.

8. The authors describe that for identification of significantly mutated genes, they applied a novel analytical methodology: MutSigCV, it will be important to know in the view of the authors, what is novel about MutSigCV tool.

Level of interest An article of importance in its field
Quality of written English Acceptable
Statistical review Yes, and I have assessed the statistics in my report.
Declaration of competing interests No competing interests.

Authors' response to reviews: (http://www.gigasciencejournal.com/imedia/1682852505161404_comment.pdf)

The reviewed version of the manuscript can be seen here:
http://www.gigasciencejournal.com/imedia/5235196031442538_manuscript.pdf
All revised versions are also available:
Draft - http://www.gigasciencejournal.com/imedia/5235196031442538_manuscript.pdf