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Sequencing of the whole human genome or determination of the
complete DNA sequence of an organism’s genome at a single time
is termed as whole-genome sequencing [ 5 ]. Capturing approxi-
mately six billion nucleotides including introns, exons, promoters,
and enhancers, whole-genome sequencing is the most compre-
hensive of the genome sequencing methods [ 1 ].
This method has the ability to discern the full range of genomic
alterations including nucleotide substitutions, copy number altera-
tions, and structural rearrangements [ 6 ]. By sufficient read depth,
whole-genome sequencing has the sensitivity to detect driver
mutations, which are present at frequencies as low as 1% of the
tumor cells [ 7 ].
Weaver and colleagues performed the first whole-genome
sequencing of 32 esophageal adenocarcinoma samples, to assess
the feasibility of initiating a large-scale project. The study reported
several recurrently mutated genes altered in esophageal adenocar-
cinoma and thus validating the ability of whole-genome sequenc-
ing to detect driver genes in the pathogenesis of esophageal
adenocarcinoma [ 4 ]. Another whole-genome sequencing study by
Dulak et al. utilizing 15 fresh frozen esophageal adenocarcinoma
tumors/nonneoplastic control pairs of tissues reported novel sig-
nificantly mutated genes SPG20, TLR4, ELMO1, and DOCK2 in
the pathogenesis of esophageal adenocarcinoma [ 8 ].
In another study, snap-frozen endoscopic mucosal biopsies
were obtained from a patient with esophageal adenocarcinoma.
This was the first example of whole-genome sequencing of matched
precursor and invasive carcinoma obtained from a single patient,
establishing the viability of using widely available and banked endo-
scopic biopsies for next-generation sequencing. The study also
reported ARID1A as a novel tumor-suppressor gene in the patho-
genesis of esophageal adenocarcinoma from Barrett esophagus [ 9 ].
Even though whole-genome sequencing is the most compre-
hensive, it is also the most expensive and creates a high amount of
redundant data [ 7 ]. While it is still relatively expensive to perform,
the costs are now approaching the level where individual patients
may be able to pay for such an approach [ 10 ].
Thus, whole-genome sequencing provides a complete charac-
terization of the esophageal adenocarcinoma genome, also it has
the potential to discover driver mutations, chromosomal rear-
rangements and study complex karyotypes [ 8 , 11 ].Exome characterizes 1% of the whole-genome region and approx-
imately 85% of disease-causing mutations are expected to occur
within the exome [ 10 ]. Whole-exome sequencing is a technique
in which only the coding regions of DNA which are of interest are
sequenced, though it is possible to target any desired region of the
genome [ 12 ]. Esophageal adenocarcinoma is heterogeneous in
nature. Whole-exome sequencing permits testing of multiple1.1 Whole-Genome
Sequencing
1.2 Whole-Exome
Sequencing
Suja Pillai et al.