Presented by Maxine Chang, ARNP, AGN, OCN2/16/2018 1 Genetics and Genomics Presented by Maxine...

2/16/2018 1

Genetics and Genomics

Presented by

Maxine Chang, ARNP, AGN, OCN

What Is Genetic Counseling? • The process of helping people understand and adapt to the

medical, psychological and familial implications of genetic contributions to disease (NSGC)

• NOT JUST GENETIC TESTING!!!

Other counselors

• Counseling offered by trained professionals other than Genetic Counselors.

• Advanced Practice Nurses certified in Genetics may offer counseling

• Registered Nurses with certification in Genetics • ARNP and Nurses are NOT considered to be Genetic

Counselors. • Counseling may be for cancer, diabetes, Alzheimer’s

disease, cardiac diseases, rare congenital diseases and reproductive issues.

Genetic Testing Options

• Single gene/syndrome testing – (e.g., BRCA1 & BRCA2)

• Multi-gene panel testing

– High-risk genes (e.g., BRCA1, BRCA2, TP53, PALB2) – Moderate-risk genes (e.g., ATM, CHEK2)

• Cost of testing is generally not a barrier to access

Who should be referred? • Diagnosed at a younger-than-typical age

– e.g., breast or colon under 50 • Multiple primary cancers

– Remote history of previous cancer(s) or synchronous cancers • Rare types of cancer

– e.g., ovarian, TNBC, male breast, pheo/paragangliomas, MTC, metastatic prostate cancer

• Family history of cancer – Each side of the family is separate

• Update testing – Previous BRCA without BART or previous testing without a panel

• Germline implications from somatic (tumor) testing

Who should be referred? • Diagnosed at a younger-than-typical age

– e.g., breast or colon under 50 • Multiple primary cancers

– Remote history of previous cancer(s) or synchronous cancers • Rare types of cancer

– e.g., ovarian, TNBC, male breast, pheo/paragangliomas, MTC, metastatic prostate cancer

• Family history of cancer – Each side of the family is separate

• Update testing – Previous BRCA without BART or previous testing without a panel

• Germline implications from somatic testing

How do I know who to refer?

• Young, rare, or not the first in the family? • NCCN guidelines • Professional practice guidelines

– ASCO (multiple guidelines/recommendations) – ACMG (Hampel, et al. Genet Med. 2015 Jan;17(1):70-87.doi:10.1038/gim.2014.147.)

• Patient request • Ask a Genetic Counselor (x3555 or genetics@moffitt.org)

L breast cancer dx 32, R breast cancer dx 34

Breast cancer dx 85 Lung Ca dx 52

TP53 Variant c.542G>A (p.Arg181His)

Case Presentation #1

Colon cancer dx 58

L breast cancer dx 32, R breast cancer dx 34

Breast cancer dx 62

Breast cancer dx 85 Lung Ca dx 52

TP53 Variant c.542G>A (p.Arg181His)

Case Presentation #1 (3 years later)

Colon cancer dx 58 TP53 Variant c.542G>A (p.Arg181His)

TP53 Variant c.542G>A (p.Arg181His)

Clinical Team Members

Clinical Geneticists (1)

Nurse Practitioner (1)

Certified Genetic Counselors (5)

Genetic Counseling Assistants (2)

Department Coordinator (1)

Dr. Xia Wang Jennifer Brzosowicz

Laura Barton

Christine Bruha Kathleen Ray

Carolyn Haskins

GeneHome Clinic Dr Xia Wang and Maxine Chang, ARNP

Katelynn Simon Jessica Metzger

Alma Tiscareno Maxine Chang, ARNP

12

• Physician oversight provided by Xia Wang, M.D., Ph.D.

• Services performed by Maxine Chang, ARNP.

GeneHome Staff

So much to learn!!!

Genes and chromosomes

DNA and RNA

What are SNPs? • SNPs are single nucleotide polymorphisms, substitutions

of one base for another that occur in more than 1% or greater in the general population.

• Difficult to identify SNPs that correlate with a particular effect in patients.

• Using SNP profiling, it may possible to tailor drug prescription and drug dosage to the individual, thereby maximizing efficacy and minimizing toxicity

SNPs continued

• This pharmacogenetic approach could save time, money,

and discomfort for millions of patients through accurate diagnoses and matching patients with appropriate medicines.

This is a SNP

Genomics vs Genetics

• The World Health Organization defines Genomics as: “the study of genes and their functions, and related techniques.”

• The main difference between genomics and genetics is that genetics scrutinizes the functioning and composition of the single gene where as genomics addresses all genes and their inter relationships in order to identify their combined influence on the growth and development of the organism.

Human Genome Project • The NIH describes the Human Genome Project (HGP) as “an

international research effort to determine the sequence of the human genome and identify the genes that it contains.”

• Coordinated by the NIH and the U.S. Department of Energy and formally began in 1990 and completed in 2003. It was scheduled to be completed in 2005 according to NIH.

• Additional contributors:- Universities across the United States, United Kingdom, France, Germany, Japan, and China.

• The HGP has revealed that there are probably about 20,500 human genes.

• All our genes together are known as our “genome.”

How have things changed?

• The work of the Human Genome Project has allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life sciences.

Genomic Medicine • The National Human Genome Research Institute (NHGRI) defines

genomic medicine as: “an emerging medical discipline that involves using genomic information about an individual as part of their clinical care (eg., for diagnostic or therapeutic decision-making) and the health outcomes and policy implications of that clinical use.”

• Oncology incorporates genomics as diagnostics for genetic and

genomic markers are increasingly included in cancer screening, and to guide tailored treatment strategies.

Pharmacogenetics

• Study of the genetic basis for variability of drug response • Genetic influences on an individuals reaction/response to

drugs or class of drugs Br J Clin Pharmacol. 2001 Oct; 52(4): 345–347.doi: 10.1046/j.0306-5251.2001.01498.x

Pharmacogenomics • Genetic considerations have been instrumental in explaining several

pharmacologic problems.

• It is a tool to assist in selecting drugs (targeted therapy), dosing of drugs (avoiding toxicity)

• Combines traditional pharmaceutical sciences with an understanding of common DNA variations in the human genome.

• The most common variations are known as single nucleotide polymorphisms (SNPs).

• Individual variations affect the drug action.

Difference Between Pharmacogenetics and Pharmacogenomics?

• Pharmacogenetics starts with an unexpected drug

response and evaluates its genetic cause, while pharmacogenomics begins with looking for genetic variations within a population that may explain certain observed responses to a therapeutic drug.

• Patil J (2015) Pharmacogenetics and Pharmacogenomics: A Brief Introduction. J Pharmacovigilance 3: e139. doi: 10.4172/2329-6887.1000e139

Safer Drugs through Pharmacogenomics

• Genes change the way medication works • Medications may be processed too quickly- therefore not

as effective. • Medications may be processed too slowly and cause

harmful effects. • Cancer treatments- • Pain medications- • Transplants (use of immunosuppressants)

Consider Cancer Treatment

Nature 429, 464–468 (27 May 2004) doi:10.1038/nature02626

Pain Medications

Personalized Medicine at Moffitt

Case Presentation #2

Breast cancer dx 40 Neurofibromas (multiple) CAL spots

Prostate cancer dx 54 Neurofibromas (multiple) CAL spots

>50 cutaneous neurofibromas, > 6 CAL spots Bilateral axillary freckling Large plexiform neurofibroma on right hip Pain level 10/10

32 yo

Specimen of neurofibroma submitted for FoundationOne testing

Case Presentation #2

Breast cancer dx 40 Neurofibromas (multiple) CAL spots

Prostate cancer dx 54 Neurofibromas (multiple) CAL spots

>50 cutaneous neurofibromas, > 6 CAL spots Bilateral axillary freckling Large plexiform neurofibroma on right hip Pain level 5/10

32 yo

FoundationOne NF1 F1708fs*, splice site 731-1G>A

Started trametinib x 4 months

OncotypeDX test report

What’s New??

Role of Nurses

• Genetics

• Education

• Patient advocacy

• Participating in research

Available training and certification • Genetics program for Nurses at Cincinnati Children's

Hospital. • Genetics/Genomics Competency Center funded by

National Institutes of Health’s National Human Genome Research Institute (NHGRI).

• Global Genetics and Genomics Community (web based). • International Society of Nurses in Genetics (ISONG). (Oncol Nurs Forum. 2015 Mar;42(2):204-6. doi: 10.1188/15.ONF.204-206.)

• Oncology Nursing Society

Take Away

• Genetics and Genomics are changing the face of

medicine.

• We should not be left behind!

• There is so much more coming- STAY TUNED.