2013-2014 Genomics in Medicine Lecture Series

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services

The 2013-2014 Genomics in Medicine Lecture Series

Suburban Hospital

This eight-lecture series by top experts in oncology and genomics will enhance health-care professionals' understanding of the intersection between genomics and medicine. The series is sponsored by the National Human Genome Research Institute (NHGRI), in collaboration with Suburban Hospital and Johns Hopkins University School of Medicine. Each lecture takes place at Suburban Hospital's lower level auditorium at 8600 Old Georgetown Road in Bethesda, Md. All are welcome to the hour-long lectures, which begin at 8 a.m. on the first Friday of the month. (Note: The June 28 lecture will start at noon. Lectures are not scheduled for July and August.) Advanced registration is not required; however, those requesting continuing medical education (CME) credits are asked to sign in.

Lectures are recorded and posted on GenomeTV and at NHGRI's YouTube channel at a later date.

For more information about the Genomics in Medicine lecture series, please contact Michelle Christ at the Suburban Hospital, mchrist@suburbanhospital.org, or Alice Bailey at NHGRI, baileyali@mail.nih.gov.

The Lectures

January 3, 2014
Kenneth H. Kraemer, M.D.
When the Lifeguard for the Gene Pool Goes on Strike: DNA Repair Disorders Xeroderma Pigmentosum and Trichothiodystrophy

Kenneth H. Kraemer, M.D.
Chief, DNA Repair Section, Dermatology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video | View Slides PDF file

DNA repair plays a major role in protecting the genome by removing DNA damage caused by sun exposure. Xeroderma pigmentosum (XP) patients with defective DNA nucleotide excision repair (NER) have a 10,000 fold increase in sunlight induced cancers of the skin (basal cell carcinoma, squamous cell carcinoma, and melanoma) and eyes. Some XP patients also have progressive neurological degeneration. Trichothiodystrophy (TTD) patients have defects in some of the same NER genes as XP patients, but their phenotype is remarkably different. Children with TTD have developmental abnormalities including congenital cataracts, absent myelin in the brain, short stature, developmental delay, multiple infections, and bone abnormalities without increased cancer. This puzzling multisystem disorder can be diagnosed by examination of their short brittle hair with a polarizing microscope revealing "tiger tail" banding of the hair shafts.

Learning objectives:
  1. Review the role of DNA repair in protection from sun damage.
  2. Understand how study of rare diseases provides information about health in the general population.
  3. Consider genetic disorders in diagnosis of unusual patients.

December 6, 2013
Electron Kebebew, M.D.
Genetics and Genomics of Thyroid Neoplasms: Moving Closer Towards Personalized Patient Care

Electron Kebebew, M.D.
Chief of the Endocrine Oncology Branch, National Cancer Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video | View Slides PDF file

Thyroid neoplasms are common in the U.S. population. Thyroid cancer is one of the fastest growing cancer diagnoses in the U.S., in part due to the increasing incidence of thyroid incidentalomas. Genetic and genomic studies have improved our understanding of the causes of thyroid neoplasms. This information is beginning to be applied to help identify the optimal diagnostic and treatment approaches in individual patients with thyroid neoplasms.

Learning objectives:

  1. Assess the change in thyroid cancer epidemiology.
  2. Review our current knowledge on the genetic and genomic changes associated with thyroid cancer initiation and progression.
  3. Consider the impact of genetic and genomic testing towards personalizing patient care.
November 1, 2013
Louis M. Staudt, M.D., Ph.D.
Practicing Precision Medicine in Cancer Using Genomics

Louis M. Staudt, M.D., Ph.D.
Deputy Chief, Metabolism Branch, National Cancer Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video | View Slides PDF file

Current classification of cancer by histology is being supplanted by molecular diagnostics based on the genomic aberrations in the tumors. The gene expression profile of a tumor and the oncogenic mutations can be used to optimize the choice of drug treatment for each patient. As applied to cancer, precision medicine will ultimately lead to combination therapy that exploits the addiction of cancer cells to constitutively active signaling pathways and other regulatory derangements.

Learning objectives:

  1. Learn how current histological classifications of cancer can be subdivided into molecularly distinct subtypes that are biologically and clinically distinct.
  2. Understand how cancers can become addicted to aberrant signaling pathways for their survival and how to target these addictions therapeutically.
  3. Understand the scientific principles underlying the choice of combination therapies based on a detailed analysis of cancer genomics and cancer cell pathophysiology.
September 6, 2013
W. Marston, Linehan, M.D.

Targeting the Genetic Basis of Kidney Cancer: A Metabolic Disease

W. Marston Linehan, M.D.
Chief of Urologic Surgery and the Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video | View Slides PDF file

Kidney cancer is not a single disease but encompasses a number of different types of cancer that occur in the kidney, each caused by a different gene with a different histology and clinical course that responds differently to therapy. Each of the seven known kidney cancer genes, VHL, MET, FLCN, TSC1, TSC2, FH, and SDH, is involved in pathways that respond to metabolic stress and/or nutrient stimulation. The VHL protein is a component of the oxygen and iron sensing pathway that regulates HIF levels in the cell. HGF/MET signaling affects the LKB1/AMPK energy sensing cascade. The FLCN/FNIP1/FNIP2 complex binds AMPK and therefore may interact with the cellular energy and nutrient sensing pathways, AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR. TSC1/TSC2 are downstream of AMPK and negatively regulate mTOR in response to cellular energy deficit. FH and SDH play a central role in the mitochondrial tricarboxylic acid (TCA) cycle whose activities are coupled to energy production through oxidative phosphorylation. Mutations in each of these kidney cancer genes result in dysregulation of metabolic pathways involved in oxygen, iron, energy, and/or nutrient sensing, suggesting that kidney cancer is a disease of cell metabolism. Targeting the fundamental metabolic abnormalities in kidney cancer provides a unique opportunity for the development of more effective forms of therapy for this disease.

Learning objectives:

  1. Learn about the different types of kidney cancer, and learn that kidney cancer is not a single disease.
  2. Learn about how to make the diagnosis of the different genetic types of kidney cancer.
  3. Learn about the kidney cancer gene pathways and learn about the current drugs targeting the kidney cancer gene pathway.
  4. Learn about the management of VHL-, HPRC-, BHD-, HLRCC-, and SDH-associated kidney cancer.

June 28, 2013
Kathleen A. Calzone, Ph.D., R.N.
Integration of Genomics into Nursing Practice

Kathleen A. Calzone, Ph.D., R.N., A.P.N.G., F.A.A.N.
Senior Nurse Specialist (Research), Genetics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video | View Slides PDF file

The clinical applications of genomics continue to expand with newly developed expectations for genomic competency of all healthcare professionals, including nurses. Nurses are an essential member of the interprofessional team in planning for clinical, policy, and delivery infrastructure that facilitates optimal translation of genomics into practice to improve health outcomes. This requires all nurses, regardless of academic preparation, role, or specialty, to achieve a minimum level of competency in genomics. This presentation will include an overview of the state of genomic healthcare applications, evidence of the existing genomic competency of the practicing nurse workforce, and strategies for achieving genomic nursing competency.

Learning objectives:
  1. Describe the relevance of genomics to nursing practice and education.
  2. Discuss three findings from the National Nursing Workforce studies which assessed attitudes, practices, receptivity, confidence, and competency in genomics of common disease and family history utilization.
  3. Explain three strategies for diffusion of genomics into nursing practice.
  4. List three resources for learning more about genomics.
June 7, 2013
Lee J. Helman, M.D.
Cancer Genomics and Precision Medicine in the 21st Century

Lee J. Helman, M.D.
Senior Investigator and Head, Molecular Oncology Section, Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video | View Slides PDF file

Major advancements in genomics technology have made affordable, rapid genome-level characterization of tumors a reality. This has in turn led to the use of genetic characterization of tumors to inform therapeutic decisions, known as "precision medicine". Importantly, cancer clinical trials are now incorporating rapid genomic characterization of tumors as selection criteria for use of specific "targeted" therapies. The approach is rapidly evolving and leading to important insights as well as creating new challenges in clinical trial design. These issues will be discussed in detail.

Learning objectives:
  1. Recognize the specific tools currently in use that allow for rapid genetic characterization of tumors.
  2. Identify ways that genetic characterization of tumors has led to specific therapeutic choices.
  3. Identify specific challenges this approach creates to carrying out clinical studies.

May 3, 2013
Neal Young, M.D., M.A.C.P.
The New Telomere Diseases: Organ Failure and Cancer

Neal Young, M.D., M.A.C.P.
Chief, Hematology Branch, and Director, Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, National Heart, Lung, and Blood Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video 

Telomeres cap the ends of linear chromosomes and protect them from damage. Telomeres shorten with every cell division, but active repair in actively replicating cells occurs by reverse transcription from an RNA template. Haploinsufficiency of TERT or TERC reduces telomerase activity and accelerates telomere attrition; mutations occur in patients with aplastic anemia, pulmonary fibrosis, and hepatic cirrhosis. Hematologic manifestations may range from subtle changes, such as erythrocyte macrocytosis and chronic thrombocytopenia, to moderate and severe marrow failure, including myelodysplasia, and also intolerance of chemotherapy. The telomere diseases are under recognized and the diagnosis is missed, due to their novelty, involvement of multiple organ systems, and the lack of commercial diagnostic tests. As patients accrue to clinics, phenotype-genotype relationships are becoming apparent. Short telomeres of leukocytes, independent of genetic lesions but likely related to regenerative stress and/or reactive oxygen species exposure, are strongly correlated to cancer susceptibility. In aplastic anemia, short telomeres strongly associate with relapse and especially evolution to myelodysplasia and acute leukemia, almost always with loss of chromosome 7 or other cytogenetic aberrations. Based on studies in humans and tissue culture models, early oncogenesis in this circumstance appears driven by chromosome instability rather than genetic alterations. Improvement in telomere regeneration may be feasible pharmacologically, and telomere measurements in the clinic should impact on diagnosis, prognosis, and treatment decisions.

Learning objectives:

  1. Understand telomere biology.
  2. Recognize telomere syndromes in the clinic.
  3. Appreciate the chromosome mechanism of oncogenesis in the setting of organ regeneration.

February 7, 2014
Thomas Ried, M.D.
Genome and Transcriptome Dynamics in Cancer Cells

Thomas Ried, M.D.
Senior Investigator and Chief of the Cancer Genomic Section, National Cancer Institute, NIH, Bethesda, Md.

YouTube video View the Lecture Video | View Slides PDF file

Chromosomal aneuploidies are observed in essentially all sporadic carcinomas. Aneuploidy results in tumor specific patterns of genomic imbalances that are acquired early during tumorigenesis, continuously selected for, and faithfully maintained in cancer cells. The presence of these aneuploidies in premalignant, dysplastic precursor lesions is strictly associated with increased progression potential to invasive disease; their detection in routinely collected cytological samples is therefore an important aspect of individualized cancer medicine. In order to dissect the immediate consequences of genomic imbalances on the transcriptome, we analyzed a large series of colon and rectal cancer using array-based genomic hybridization and gene expression profiling. Our results support the interpretation that malignant cells carry two specific and concurrent alterations of the cellular transcriptome. The first involves low-level expression changes of many or most genes that reside on chromosomes that are gained or lost. Such a ploidy-driven transcriptional deregulation results in the increased expression of genes involved in RNA- and cellular metabolism. Increased expression of these genes could therefore render an early proliferative advantage to cells carrying aneuploidies. The second alteration is the gain or loss of function of specific oncogenes or tumor suppressor genes, respectively. We observed such a pattern also in murine models of epithelial tumorigenesis that we established using spontaneously immortalized and transformed cells.

Learning objectives:
  1. Review the role of genomic imbalances in solid tumors.
  2. Understand how aneuploidy affects the transcriptome of cancer cells.
  3. Appreciate how aneuploidy can serve as a molecular marker for improved diagnosis and prognostication.

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Last Updated: February 12, 2014