Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 1
1
Introduction
1
The initial sequencing of the human genome, carried out by an inter-
national group of experts, took 13 years and $2.7 billion to complete. In
the decade since that achievement, sequencing technology has evolved at
such a rapid pace that today a consumer can have his or her entire genome
sequenced by a single company in a matter of days for less than $10,000,
though the addition of interpretation may extend this timeframe. With the
next-generation sequencing technology currently being developed, the cost
is projected to continue to decline significantly over the next few years, to
the point that large-scale genome sequencing is expected to become com-
parable in cost to a single gene test or to a diagnostic imaging test such as
a computed tomography (CT) scan (Mardis, 2006).
Given the rapid technological advances, the potential effect on the lives
of patients, and the increasing use of genomic information in clinical care,
it is important to address how genomics data can be integrated into the
clinical setting. Genetic tests are already used to assess the risk of breast
and ovarian cancers, to diagnose recessive diseases such as cystic fibrosis,
to determine drug dosages based on individual patient metabolism, and to
identify therapeutic options for treating lung and breast tumors, melanoma,
and leukemia.
Recent studies have also demonstrated the usefulness of genomics for
diagnosing disease and guiding treatment in the clinic. For example, genetic
1 The planning committee’s role was limited to planning the workshop, and the workshop
summary has been prepared by the workshop rapporteurs as a factual summary of what
occurred at the workshop.
1
OCR for page 2
2 INTEGRATING LARGE-SCALE GENOMIC INFORMATION
testing of the relatives of patients newly diagnosed with colon cancer
has suggested a prevention strategy for identifying individuals with Lynch
syndrome (Coates et al., 2011). Genomics data have been used to pro-
vide definitive diagnoses for patients with neuropathy, inflammatory bowel
disease, and Proteus syndrome as well as to guide therapeutic care for
patients with arterial calcifications, movement disorders, and Miller syn-
drome (Bainbridge et al., 2011; Lindhurst et al., 2011; Lupski et al., 2010;
Ng et al., 2010; St. Hilaire et al., 2011; Worthey et al., 2011). Although
applications of genomics technologies are currently limited in number, their
number will only continue to increase. Thus, it is important to determine
how genomic data can best be integrated with clinical practice so as to
maximize patient benefit. As Bruce Blumberg from Kaiser Permanente
observed in the workshop, “During the year in which we plan[ned] the
workshop, the future became the present.” It became increasingly clear, he
said, that large-scale genomic information would be integrated more fully
into clinical practice, which meant that issues related to implementing this
change needed to be addressed.
Using DNA sequencing data on a large scale in a clinical setting will
pose many difficult challenges. The storage, access, and portability of
genetic data all raise significant issues. Questions exist about the need for
confirmatory testing of results within a Clinical Laboratory Improvement
Amendments (CLIA)–certified laboratory. Relevant information will need
to be extracted and deposited into the appropriate medical records in a
clinically comprehensible manner. The analysis of this information—and re-
analysis as new findings emerge—will put further constraints and burdens
on health care practitioners and laboratories, particularly as the current
health care system lacks a mechanism to reimburse these activities. Ethical
issues related to such things as informed consent and stewardship over this
information will also need to be considered as integration moves forward.
Complicating all of this is the fact that most patients and health care pro-
viders have not yet realized just how broad an effect genomic discoveries
are likely to have on treatment course and health.
With these issues in mind and considering the potential impact that
genomic information can have on the prevention, diagnosis, and treatment
of disease, the Roundtable on Translating Genomic-Based Research for
Health hosted a workshop on July 19, 2011, to highlight and identify the
challenges and opportunities in integrating large-scale genomic informa-
tion into clinical practice. The workshop was premised on the assumptions
that sequencing technology will advance to the point that it can produce
clinically meaningful results and that whole-genome sequencing will be
cost-effective and comparable in cost to other diagnostic tests. There is little
point in deliberating about these assumptions, Blumberg said, because “no
OCR for page 3
3
INTRODUCTION
matter what the outcome of our debate . . . this is going to happen. This is
already happening.”
The planning committee for the workshop decided early in its discus-
sions that a single workshop would be insufficient to adequately address
every issue, challenge, or opportunity related to clinical genomic medicine.
Therefore, to begin a discussion about the use of genomic data in the
clinic, the workshop committee decided to focus on several key topics,
including the analysis, interpretation, and delivery of genomic informa-
tion to health care providers plus workforce, ethical, and legal issues. This
workshop report summarizes the speakers’ presentations and the discus-
sions that followed them. It begins by providing an overview of the current
state of the field of genomic medicine, of how approaches to basic and
clinical research are changing, and of areas in which steps can be taken
immediately to build the necessary infrastructure (Chapter 2). The next two
chapters describe the discussions that took place concerning the analysis
and interpretation of genomic data (Chapters 3 and 4), while the following
three chapters examine practical issues: the delivery of genomic informa-
tion (Chapter 5), ethical and legal issues (Chapter 6), and developing the
necessary workforce skills and knowledge (Chapter 7). The last chapter
describes panel discussions on how to maintain curated databases, the role
of the field in public health, and how each stakeholder could be involved
in helping address the current challenges (Chapter 8).
The main objective of this workshop was to start a discussion of what
needs to be done to prepare the necessary infrastructure and to address the
various challenges so that patients will be able to benefit from genomics-
based research. As Catherine Wicklund from Northwestern University said,
the realization that genomics data can be useful in the clinic “is here and
we really need to deal with this issue.”
OCR for page 4
