The Journal of Molecular Diagnostics, Vol. 15, No.

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.

Next-generation sequencing methods provide an opportunity for molecular pathology laboratories to

perform genomic testing that is far more comprehensive than single-gene analyses. Genome-based test
results are expected to develop into an integral component of diagnostic clinical medicine and to provide
the basis for individually tailored health care. To achieve these goals, rigorous interpretation of highquality data must be informed by the medical history and the phenotype of the patient. The discipline of
pathology is well positioned to implement genome-based testing and to interpret its results, but new
knowledge and skills must be included in the training of pathologists to develop expertise in this area.
Pathology residents should be trained in emerging technologies to integrate genomic test results
appropriately with more traditional testing, to accelerate clinical studies using genomic data, and to
help develop appropriate standards of data quality and evidence-based interpretation of these test results.
We have created a genomic pathology curriculum as a rst step in helping pathology residents build
a foundation for the understanding of genomic medicine and its implications for clinical practice. This
curriculum is freely accessible online. (J Mol Diagn 2013, 15: 141e148; http://dx.doi.org/10.1016/
j.jmoldx.2012.11.003)

Data gathering and contextual interpretation of results form

the core of the discipline of pathology. As in most areas
of diagnostic medicine, expert knowledge in pathology
combines the ability to decide what types of investigation
should be performed and which ndings or results should be
prioritized in arriving at an accurate diagnosis. A detailed
understanding of the limitations of laboratory testing methods
and the signicance of results in the clinical context of the
patient are equally important. Thus, objective information
from diagnostic tests is ltered through a knowledge base of
human diseases and their manifestations in a process that is
still probably best described as part of the art of medicine.
Good clinical care has always been personalized in the
sense of viewing clinical and laboratory data in light of the
patients specic history, current signs and symptoms, habits,
behaviors, and family or socioeconomic settings. Genome
sequencing for individual patients, particularly if analyzed
together with the transcriptome (the collection of RNA
Copyright 2013 American Society for Investigative Pathology
and the Association for Molecular Pathology.
Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jmoldx.2012.11.003

species expressed from the genome), proteome (the protein

species present in the cells or uids of the body), and
metabolome (the set of small molecules taking part in the
metabolic and signaling pathways of the body) of the patient,1
differs only in the sheer amount of objective, highly detailed
new data that will be made available for clinical interpretation.
It is likely that large amounts of additional clinically relevant
information will become available by performing detailed
analyses of the microbiomes of the patient, those populations
of microorganisms in residence in various anatomical sites
throughout the body that can have a diversity of effects on
health and disease.2,3 In this article, unless otherwise specied, references to genomic testing are meant to include not
only the results of analysis of the genome but also the
downstream -omes consisting of the transcriptome, proteome,
and metabolome. For medical conditions in which genetic
Supported by the Stanford Pathology Department.

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,

2012)]. Although such education should begin with medical

students, it must also be provided at the residency and
fellowship training levels. This training is particularly important for current and future pathology trainees, who will be
central to the diagnostic process and interpretation of laboratory test results. Ultimately, genomic information also needs to
be disseminated and made accessible to other groups, such
as policy makers, nonphysician health care providers, and
patients and their families.6
Pathology training programs need to identify the optimal
route for pathology trainees to engage with the subject matter
and methods of genomic medicine. The need for such
curricula is widely recognized, but they are not yet offered in
most pathology residency programs.7 The need to introduce
genomic concepts and knowledge into the curriculum of
medical and graduate schools has also been recognized, and
innovative approaches are being tried.8e12 However, we think
that the specialty of pathology is where the application of new
assay technologies, the interpretation of the new data they
provide, and the integration of such data with that derived
from the other laboratory diagnostic methods must be
implemented in clinical practice. The rst pathology residency curriculum in genomics and personalized medicine to
be published included a lecture on personal genomics, another
on high-throughput sequencing, and a third on interpreting
genetic risk.13,14 This didactic curriculum was supplemented
by a voluntary opportunity for residents to obtain limited
personal genotyping of single nucleotide polymorphisms by
three commercial personalized genomics companies and to
perform subsequent interpretation of their own risk factors. In
addition, the collaborative intersociety Training Residents in
Genomics Working Group has made available four lectures to
enhance the education of pathology residents in genomics in
the context of an existing curriculum in molecular pathology
at individual programs (Intersociety Council for Pathology
Information Inc., http://www.pathologytraining.org/trig_
lecture.htm, last accessed October 10, 2012). These lectures
include genomic methods, clinical interpretation of genomic
testing, and communicating and reporting genomic test
results. Recently at Stanford, we developed a 2-year genomic
pathology curriculum based on a core of 10 didactic lectures
in the rst year and a second-year course of more advanced
topics, with opportunities for data interpretation of educational samples.
Recognizing that new genomic methods build on a substantial background of genetic studies and genotype-toe
disease phenotype correlations painstakingly accumulated
over previous decades, our curriculum reviews the conventional literature so that trainees understand earlier methods
and results well, including major disease-associated DNA
sequence variants in cancer and inherited disorders. For some
trainees, this lecture serves as a refresher of previously
acquired information, whereas for others with less molecular
background training, this is an essential foundation review. In
addition, focused didactic sessions describe new methods for
DNA sequencing and sequence data analysis, with

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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

Consensus guidelines: new diagnostic categories;

prognostic information, treatment regimens,
and monitoring of health and disease, tailored to the individual

illustrations of clinically validated conclusions for the medical

relevance of particular sequence variants. Further lectures
address subspecialty areas in which genomic medicine is expected to have a direct effect on routine clinical practice,
including hematopathology, transplant pathology, and
surgical pathology.
The biggest challenges for faculty educators include the
ability to keep pace with the fast-moving technological and
conceptual developments in the eld and to present
a complex subject matter in cogent ways so as to complement current knowledge with the likely clinical relevance of
genomic medicine for the future practice of pathology. A
genomics-based curriculum today offers a window into the
fast-approaching future, in which this knowledge will transition from the domain of research and become a routine
part of clinical practice. Similar transitions in our eld have
occurred in the past, as when dramatic revisions of

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Toward clinical implementation of

a personalized genomic medical evaluation. In
addition to learning about the new tools,
methods, and data from genomic science, and the
fundamental knowledge of human genetics that
preceded them, residents learn the importance of
integrating genomic data with the results of
traditional clinical phenotyping of the patient,
including bedside history and physical examination; radiologic and other imaging studies; laboratory tests measuring small molecules, levels of
expressed RNA, and proteins; and histologic,
cytologic, and immunophenotypic evaluation of
blood, body uid, and tissue biopsy samples, as
well as microbiologic assessment of the microbiomes of the patient. The study of paired
genomic and phenotypic data from sufcient
numbers of patients offers the best opportunity
for deriving medical knowledge that can be used
to attempt to interpret the signicance of sequence variants in the genome of an individual. A
combination of retrospective studies and new
prospective clinical trials and other studies
incorporating genomic data will be needed to
assess the potential benets and costs of guiding
management and therapy choices based on
a medical evaluation of the patient that includes
genomic ndings. Over time, new consensus
guidelines incorporating genomic data will be
dened by appropriate expert panels. Progress in
this new area of medicine will undoubtedly be
inuenced by factors external to the diagnostic
laboratory, such as federal and state legislative
actions, regulatory bodies, and the activities of
the private sector, including insurers, diagnostic
companies, pharmaceutical companies, and
patient advocacy groups. Residents can expect to
see signicant changes in all of these areas during
their training and as they enter independent
clinical practice.

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

Description of the Genomic Medicine Course

The Department of Pathology at Stanford University developed an annual course in genomic medicine for all of its
residents and fellows, as part of its required core educational
curriculum for all AP and CP residents, which began in the
2010-2011 academic year and has continued to the present.
Interested faculty members are also encouraged to attend the
lectures. This course is intended to provide a broad basis for
understanding the rapid developments in genomic medicine
and is designed to help prepare our residents for pathology
practice in which genomic medicine is an integral part of
medical diagnosis and patient care. The course provides an
overview of the fundamental principles of molecular
biology, clinical genomics, and personalized medicine and
of current and evolving research and clinical applications
(Table 1). Ethical and legal ramications and regulatory
considerations pertaining to this increasingly comprehensive
approach to diagnostic testing and predictive medicine are
also being addressed.

Genomic Medicine Core Curriculum

The course directors (Department of Pathology faculty
members involved with resident education and genomic
medicine) developed a core curriculum in genomic medicine,
with speakers from a variety of diagnostic specialty areas.
The course consists of a didactic series of 10 lectures and
provides an overview of the most pertinent research and
clinical translation topics in clinical genomic testing. The
course was developed according to the core competencies
identied by the Accreditation Council for Graduate Medical
Education and includes focused learning in the areas of
patient care, practice-based improvement, communication,
professionalism, medical knowledge, and health care

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delivery (Core Competencies, http://med.stanford.edu/gme/

current_residents/corecomp.html, last accessed November
28, 2012). The competencies of medical knowledge and
patient care are interwoven into every lecture. The competency of practice-based learning and improvement is met
through the investigation and evaluation of current and
anticipated applications to patient care and through appraisal
and assimilation of scientic evidence. The competency of
interpersonal and communication skills is supported through
opportunities for comments, questions, and further discussion. Professionalism is fostered through integration into the
lectures of ethical principles and socioeconomic considerations. Finally, the competency of systems-based practice is
a core component of the course given the coverage of
potential effects on the health care system and on health care
resources. Each lecture is freely available on the Internet
(Stanford Open Curriculum in Genomic Medicine, http://
www.youtube.com/watch?vZFybGAH5IDZk&listZPLfTljt
R5bxMcTg8hgQp9sA4YQwicpSAQv, last accessed October
10, 2012) and has a set of learning objectives, as outlined in
Table 1. We created this series with broad coverage of
fundamental topics in genomics in mind while also leaving
room for the inclusion, in each of the subspecialty-oriented
lectures, of the most pertinent and clinically applicable
points in that subspecialty area. Bioinformatics and concepts
pertaining to the analysis of complex data sets are incorporated throughout the series and are particularly emphasized in
the lectures on the fundamentals of human genetic variation,
microarrays and analysis of hybridization data, and DNA
sequencing and high-throughput DNA sequencing methods.
The lectures present examples from the recent literature
that illustrate how next-generation methods can be used for
discovery and how similar approaches are being explored
for application in the clinical setting. As one example, nextgeneration methods are being used in cancer genomics to
discover connections between relevant pathways in cancer
cells and to more completely identify the spectrum of
mutations that can be associated with each subtype of a solid
tumor or at different stages of the evolution of the tumor.
Currently, the number of clearly interpretable mutations is
still relatively small, although this number is increasing
rapidly. Such information may substantially change the
diagnostic subclassication of these tumors, and also help in
the development of individualized treatment regimens for
patients with cancer.

Elective Course in Advanced Genomic Medicine

The second course, a curriculum in advanced genomic
medicine, began in the 2011-2012 academic year. This
course provides a more in-depth curriculum for residents,
fellows, and faculty and is taught as an elective (Table 2).
The curriculum is specically created to enable interactive
learning in a small group setting, addressing topics such as
computational and statistical methods relevant to analysis of
DNA sequence data, including genomic data. This elective

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is targeted toward participants who plan to work actively
with genomic data, use genomic sequence interpretation
tools, and participate in genomic testing for research and
clinical purposes. Because of the small group setting and
more interactive nature of the elective course, this course is
not currently available online.
Much as graduate students and postdoctoral fellows
working in many areas of biological research now must
become at least familiar, if not procient, with computational methods for dealing with large data sets, including
DNA sequence data sets, we believe that pathology residents and fellows benet from learning about the algorithms
for aligning nucleic acid sequences and from detecting and
interpreting the wide range of medically relevant sequence
variants. Several sections of the second-year curriculum
address these topics, provide greater detail about the new
technologies being applied to measure DNA sequences
(including the kinds of errors or artifacts generated by
different instruments), and permit more in-depth discussion
about human genetic variation than is covered in the rstyear lecture. Explanations of sequence alignment algorithms
and approaches for detecting sequence variants in highthroughput DNA sequence data sets include earlier algorithms, such as the Smith-Waterman and BLAST algorithms,
as well as discussion of current mapping algorithms for
genomic sequence data.
Competent interpretation of medical DNA sequencing
data cannot simply treat sequence analysis as a black box
dealt with by commercial software packages. The knowledge and skills, including familiarity with computer programming, helpful for dealing with such data are different
from the visual interpretation skills that form the basis of
histologic pathologic diagnosis, yet they are routine in other
highly trained professions, such as engineering, and can
certainly be learned by motivated physicians. Indeed,
development of the skills of histologic interpretation within
the specialty of pathology or of interpretation of radiologic
images in radiology already distinguish these diagnostic
specialties from much of the rest of medicine and form
a precedent for the learning of new skills needed to take
advantage of the latest technological innovations in DNA
sequence analysis. The medical director of a clinical
chemistry laboratory does not need to be an expert synthetic
research chemist, but a rm understanding of chemical
principles and reactions involving biological molecules is
required for effective functioning and troubleshooting in
that role. Something similar should be the expectation for
pathologists involved in the interpretation of genomic
sequence data and is the direction that our second-year
curriculum attempts to encourage for current trainees.

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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systems or disease mechanisms, and the eld of pathology is

no exception. Throughout this time, new diagnostic methods
have been incorporated into the routine practice of pathology.
Although the broad eld of pathology still relies heavily on
visual interpretation, such as that of histologic analysis and
immunohistochemical staining in anatomical pathology and
interpretation of karyotypes in the clinical cytogenetics
laboratory, additional specialty areas and new methods have
complemented the traditional skill set with training in the
generation and interpretation of numerical and quantitative
data. This is particularly true in molecular pathology and
seems likely to expand greatly with genomic medicine testing
methods.
In contrast to the interpretation of images, genetic information is most naturally represented as linear textual data (ie,
DNA sequences) and uses syntax and encoding that are not
necessarily obvious to either the human eye or brain. Most
current molecular pathology tests assess a small number of
gene sequence variants. Knowledge of these variants and
their associations with disease or other phenotypes, such as
drug sensitivity, represents a manageable number of facts.
New genomic analytical methods, however, will incorporate
vastly larger sets of DNA sequence variants from germline
and tumor cell genomes, many of which are of, as yet,
unknown clinical signicance. The number of mutations
with correct annotation and validated medical interpretations
can be expected to steadily grow over time, although
substantially more slowly than the amount of data that will
be generated through high-throughput DNA sequencing
methods. In the case of cancer-related mutations, it remains
to be seen how many genes will be frequently mutated in any
given cancer and whether combinations of several or many
very rare mutations will turn out to be essential to the
pathogenesis of some tumors.
Apart from assessing the adequacy of sequencing depth
and coverage, analysis of genomic sequence data from large
numbers of clinically well-characterized patients will probably be necessary to identify the sequence variants relevant to
pathogenesis, prognosis, and therapeutic responses. Analysis
of such large data sets typically requires knowledge of
computer programming and a detailed understanding of the
strengths and weaknesses, including characteristic artifacts, of different sequencing technology platforms. Most
current trainees and faculty in pathology departments, as
well as practicing pathologists in other settings, do not have
strong quantitative analytical skills or computational
backgrounds. Future trainees and motivated pathologists in
academia and the private sector should give serious thought
to putting in the effort to improve their data analysis and
programming abilities. This could be accomplished, for
example, through bioinformatics graduate training or new
fellowships within pathology. Such training is expected to
lead to a highly sought-after skill set. A course of lectures
such as that of our new online curriculum and the elective in
advanced genomic medicine may also help toward this end,
but it is probable that partnerships with bioinformaticists

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Table 1

Overview of the Stanford Open Didactic Core Curriculum in Genomic Medicine

Lecture No. Description

1

Experimental methods for measuring and manipulating DNA/RNA

The rst lecture provides an overview of the close linkage between technological tools for studying nucleic acids and the
discoveries in biology and medicine enabled by them. By the end of the lecture, participants should understand:
1. The chemical structure of DNA and RNA and how this determines the stability and functional activity of
these molecules
2. Assays based on hybridization to detect particular DNA or RNA molecules
3. DNA/RNA-manipulating enzymes and molecular cloning methods
4. The polymerase chain reaction and related methods
5. The different technologies used to determine the sequence of DNA and RNA
6. Insights that gene sequence data have given in medicine, and the current limits of that knowledge
Fundamentals of human genetic variation
This lecture provides an overview of features of the human genome: protein-coding genes, noncoding genes, and gene-poor
regions of the genome. It includes discussion of what is known of how different human populations and individuals
differ from each other genetically and addresses consequences for health and disease. By the end of the lecture,
participants should understand:
1. The size, structural features, and organization of the human genome; comparisons with other genomes from model
organisms in which disease-related studies have been performed
2. Key features of protein-coding genes and how these relate to gene regulation and mechanisms of disease
3. Kinds of noneprotein-coding genes and their proposed functions
4. Ways in which the genome is modied and controlled (covalent modications of DNA, chromatin alterations, and DNAinteracting proteins)
5. Major types of genomic variation among different human populations and individuals and some examples of how these
relate to diseases
Microarrays and analysis of hybridization data
This lecture provides a review of the rst highly parallel assays for gene expression and DNA copy number. By the end of the
lecture, participants should understand:
1. Different kinds of microarray technologies (array fabrication and experimental methods) that have been used for mRNA
or DNA measurements
2. Mathematical methods that can be applied to highly parallel assay data to study relationships among different
biological samples
3. New disease classications and insights that arose from microarray data measuring mRNA expression
4. DNA copy number assays and medical applications of these
DNA sequencing and HTS
This lecture addresses current HTS methods and possible future methods. By the end of the lecture, participants should
understand:
1. Sequencing-by-synthesis methods (pyrosequencing and other approaches)
2. Hybridization-based methods
3. Single-molecule, nonamplied approaches
4. Single-tag versus paired tag and multiple tag approaches; advantages and limitations of each
5. Basic kinds of algorithms used to analyze HTS data (mapping reads onto reference genome, discovering variants)
6. Economics of genome sequencing using these methods
Inherited genetic disorders
This lecture provides a review of inherited genetic disorders, including structural genome changes, with discussion of
databases and resources and diagnostic utility of conventional methods versus next-generation approaches. Several
articles are highlighted as examples of practical utilization. By the end of the lecture, participants should understand:
1. Mendelian inheritance patterns and complications
2. Structural genomic variation
3. Conventional and novel methods for diagnosing inherited genetic disorders
4. Traditional ways of identifying genes associated with disease
5. Next-generation methods (exome analysis and whole genome analysis) used for the identication of mutations and
genes associated with disease
Acquired mutations in human cancers I: solid tumors
This lecture provides an overview of genetic lesions in solid tumors. By the end of the lecture, participants should
understand:
1. Translocations and other mutations found in sarcomas; pathways or mechanisms thought to be affected by these
2. Genetic lesions found in carcinomas; pathways or mechanisms thought to be affected by these
3. Whole genome sequencing of solid tumors and conclusions from these initial efforts
(table continues)

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Table 1 (continued )
Lecture No. Description
7

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.

and with pathologists and other colleagues who have taken

additional training in computational methods will be a key
practical step for many academic departments and private
sector groups in the near-term. Going forward, however, it
seems likely that a subset of pathology trainees would
benet from spending as much time and effort in learning
bioinformatics, computational methods, and statistics as is
currently spent learning the complexities of the various
disciplines of anatomical and clinical pathology. To this
Table 2 Topics in the Elective Course in Advanced Genomic
Medicine
1
Next-generation sequencing methods 2.0
2
Human genetic variation 2.0
3
DNA sequence analysis methods I: sequence databases and
les
4
DNA sequence analysis methods II: sequence alignment
algorithms
5
DNA sequence analysis methods III: genome assembly and
analysis
6
Introduction to scripting programming languages
7
Statistical tools for sequence analysis and genomics

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end, the development of subspecialty fellowship training

that offers additional training in computational methods
and genomic applications to address these needs may
become necessary in the near future.
The new era of genomic testing and diagnosis may
provide other challenges and opportunities. For example, it
may be helpful for medical centers to establish regularly
scheduled clinical conferences in which pathologists and
colleagues who directly interact with patients come together
to interpret genomic data in the context of the clinical
ndings of the patient, other laboratory data, and imaging
studies. The multidisciplinary team would conrm and
rene diagnostic classication, assess disease heterogeneity,
evaluate for known drug targets and variant susceptibilities,
assess prognosis, and attempt to tailor clinical management
with the guidance of all data available for each patient. We
think that appropriately trained pathologists should be able
to play a central role in secondary or tertiary inpatient health
care informed by genomic testing and in interpretation of
genomic sequence data in the primary care context, perhaps
even before diseases manifest.6 Rigorous genomics training
is critical to help prepare pathology residents to interpret

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genomic information and to help multidisciplinary health
care teams apply these new data for optimal patient care.

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References

The Journal of Molecular Diagnostics