2, March 2013
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SPECIAL ARTICLE
Integration of Genomic Medicine into Pathology
Residency Training
The Stanford Open Curriculum
Iris Schrijver,*yz Yasodha Natkunam,* Stephen Galli,*zx and Scott D. Boyd*z
From the Departments of Pathology* and Pediatrics,y Stanford University School of Medicine, Stanford; and the Center for Genomics and Personalized
Medicinez and the Departments of Pathology and Microbiology and Immunology,x Stanford University Medical Center, Stanford, California
Accepted for publication
November 28, 2012.
Address correspondence to
Iris Schrijver, M.D., Department
of Pathology, L235, Stanford
University School of Medicine,
300 Pasteur Dr., Stanford,
CA 94305. E-mail: ischrijver@
stanfordmed.org.
Schrijver et al
factors play a signicant role, and to the extent that clinically
meaningful interpretation of the new genomic and other
-omics data, including analyses of microbiomes, will inuence
the prediction, detection, diagnosis, classication, monitoring,
management, or treatment of illness, the approaching era of
genomic medicine offers great hope for improvements in
patient care.
Initial analyses of whole or partial genome sequences from
patients and diseased tissues, such as cancers, have begun to
test the scale of the obstacles that must be overcome to enable
improved detection, classication, and prognostication of
diseases, together with better treatment selection and therapeutic response monitoring. It would be fair to say that
genomic analysis of human disease is in its infancy. Published studies have analyzed only a small fraction of the data
generated by genome sequencing, typically simplifying
analyses by focusing on i) only exonic or splice site mutations in human tumors, ii) correlations with genome-wide
association study results or with the relatively small databases of mutations with known phenotypic effects discovered
before the genomics era, or iii) medically compelling but
relatively uncommon conditions, such as mendelian genetic
disorders.
Almost as complicated as the human genome itself is the
constellation of scientic, technical, legal, ethical, regulatory,
and clinical practice elements that must be appropriately
aligned to make the medical use of genome information safe,
reliable, and practical (Figure 1). One challenge will be to
achieve thoughtful integration of rapidly evolving scientic
and bioinformatics technologies with well-designed basic and
translational research while keeping in mind the pragmatic
concerns of clinical practice. Another will be to succeed in
dealing with the larger legal, ethical, and economic frameworks that impact any change in clinical medicine. Meeting
these challenges will likely involve partnerships among
academic, governmental, private sector, and patient advocacy
interests. Targeted federal research funding in these topics,
together with appropriate health care legislation and policies
that aim to put the interests of the patient rst, will be critical in
realizing the potential of recent genomic and other -omics
technology innovations.
Another important step will be the education of a new
generation of pathologists who are familiar with the scientic
and medical background and with other aspects of the genomic
testing environment (Figure 1) and who are equipped to apply
genomic methods in translational research and, eventually,
clinical practice. More broadly, to build a foundation in
genomic medicine for all practicing physicians, we think that
genetics and genomics courses must start early in the medical
school curriculum and be incorporated into practice-based
learning rather than merely taught in the basic science
curriculum.4 Pilot projects are currently being explored in
medical schools [eg, Tufts University School of Medicine5 and
Stanford University School of Medicine (The Deans Newsletter: September 28, 2009, http://deansnewsletter.stanford.
edu/archive/09_28_09.html#1, last accessed October 10,
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Genotyping:
whole genome
or exome
sequencing
Laboratory
phenotyping:
current laboratory
tests, transcriptome,
proteome,
metabolome,
microbiome,
etc.
Figure 1
Clinical
phenotyping:
history, physical
exam, imaging,
histology,
etc.
Personalized
genomic
medical
evaluation
Clinical
trials with
genomic
medical data
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hematologic disease classications were enabled by immunophenotypic, cytogenetic, and molecular methods.15e22
We think that incorporation of genomic medicine into
pathology training curricula should begin immediately to
better prepare residents for their future practice. It should be
added to, and not take the place of, general anatomical and
clinical pathology training to ensure the continuing development of a broad pathology knowledge fund that remains
essential to the assimilation of information regarding all
aspects of the disease of the patient and to arrive at
a comprehensive, informed diagnosis (or diagnoses). Naturally, a training curriculum in genomic medicine will serve
only as a foundation for further learning, for example,
through fellowship training, by pathologists who will actively
and directly engage in interpreting these tests in the future.
Early exposure of all pathology trainees to the methods and
results of genomic medicine will, nonetheless, help position
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a future generation of pathologists to embrace fully the
challenge of providing clinically relevant interpretation of the
vast amounts of data generated by these methods and to
become the recognized experts in this diagnostic area. Much
of genomic medicine is still in the realm of research but is
likely to transition rapidly to clinical practice as soon as
validated, and clinically actionable, applications have
become established in the peer-reviewed scientic literature
(ideally, with signicant contributions from clinical trials
designed with genomic data sets in mind). Expecting
immediate consensus or waiting for other elds of medicine
to solve these scientic and diagnostic challenges would, in
our opinion, constitute a missed opportunity. The discipline
of pathology is uniquely positioned to play a central role in
how genomics is incorporated into medicine. Early education
of pathology residents in genomic methods will serve
them, their patients, and the profession well, whether these
trainees eventually work in community practice, industry, or
academia.23
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Discussion
As a result of the explosion of medical knowledge in the 20th
century, much of medicine is now subspecialized by organ
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Table 1
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10
Pharmacogenomics
This lecture provides a background in pharmacogenomics for pathology residents, who do not prescribe medications as part
of their usual medical practice. By the end of the lecture, participants should understand:
1. Major pathways of drug absorption and distribution and genetic variations that affect these
2. Major pathways of drug metabolism and genetic variations that affect these
3. The currently known mutations that are the most clinically important for patient management
4. The limits of pharmacogenomic predictions made using current data
HLA genetics
This lecture provides a review of HLA and clinical implications of HLA typing as well as the possibilities for integration of
next-generation sequencing methods. By the end of the lecture, participants should understand:
1. The structure and genes of the HLA loci in humans
2. Clinical settings in which HLA typing and matching are required and the clinical impact of varying degrees of matching
3. The advantages and disadvantages of new locus sequencing methods compared with established serologic and cellular
assays for HLA typing
Acquired mutations in human cancers II: hematopoietic malignancies
This lecture provides an overview of genetic lesions in hematopoietic malignancies. By the end of the lecture, participants
should understand:
1. Major translocations found in lymphoid neoplasms; pathways or mechanisms thought to be affected by these
2. Major translocations found in myeloid neoplasms; pathways or mechanisms thought to be affected by these
3. Point mutations and small lesions in acute myelogenous leukemia
4. Mutations in myeloproliferative neoplasms
5. Whole genome sequencing of hematopoietic malignancies and conclusions from these initial efforts
Personal genomics: commercial
This lecture covers new businesses and health care paradigms involving determination of genetic information for customers
or patients, with or without involvement of the medical profession. By the end of the lecture, participants should
understand:
1. New personal genetics/genomics companies, the methods they use, and the kinds of data and interpretations they
provide
2. The current role of genetic counseling in medicine
3. Regulatory issues precipitated by the new personal genetics/genomics and direct-to-consumer companies
4. Medical, economic, and ethical considerations raised by new whole genome sequencing methods in the US health care
system
HTS, high-throughput DNA sequencing.
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genomic information and to help multidisciplinary health
care teams apply these new data for optimal patient care.
12. Thurston VC, Wales PS, Bell MA, Torbeck L, Brokaw JJ: The current
status of medical genetics instruction in US and Canadian medical
schools. Acad Med 2007, 82:441e445
13. Haspel RL, Arnaout R, Briere L, Kantarci S, Marchand K, Tonellato P,
Connolly J, Boguski MS, Saftz JE: A call to action: training pathology
residents in genomics and personalized medicine. Am J Clin Pathol
2010, 133:832e834
14. Haspel RL, Arnaout R, Briere L, Kantarci S, Marchand K, Tonellato P,
Connolly J, Boguski MS, Saftz JE: A curriculum in genomics and
personalized medicine for pathology residents. Am J Clin Pathol 2010,
133:online supplement
15. Cleary ML, Chao J, Warnke R, Sklar J: Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl
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Arch Pathol Lab Med 2009, 133:605e610
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References