Table 1

Challenges for translating high-throughput sequencing into clinical oncology.

Which patients could benefit?Focus evaluation on patients with
advanced refractory cancer
who are considering clinical trials.
Focus evaluation on patients
with rare, poorly defined disease
with no standard therapy.
How will informed consent
for integrative sequencing
be obtained? How will incidental
findings be dealt with?
Consent through a flexible default
consent form, developed in
conjunction with bioethicists and
genetic counselors, which includes
up-front genetic counseling,
discussion of risks for incidental
findings, and preservation of
patient autonomy to accept or
decline learning about incidental
What type of sequencing should
be performed?
Assess comprehensively and
cost-effectively tumor structural
rearrangements, copy number
alterations, point mutations,
insertions, deletions, and gene
How will the computational
analysis be completed
for each patient?
Rapidly assess data and provide
orthogonal support for calling
mutations with multiple
bioinformatics pipelines.
Focus analyses on genes that could
have known clinical significance
including genes used in best
clinical practices, identified as
tumor suppressors or oncogenes
through the Sanger Cancer
Census, and all potentially
druggable kinases.
How will sequencing be completed
within a clinically relevant
time frame?
Complete integrative sequencing
within 4 weeks to match the
typical time frame that patients
must wait between oncology
clinical trials.
How will results be interpreted?Assemble multidisciplinary team for
a Sequencing Tumor Board with
expertise in clinical oncology,
clinical genetics, genomics,
bioinformatics, clinical pathology,
social and behavioral sciences,
and bioethics.