Genetic Disorder Reference Sheet: BARD1
Located on chromosome 2 with 11 exons, BRCA1-associated ring domain (BARD1) is part of the BRCA1/BARD1 protein complex and associated with breast cancer susceptibility. The protein complex enhances ubiquitin ligase activity, which helps regulate centrosome function, repair DNA, and regulate cell cycles to maintain genetic stability. BARD1 interacts with and stabilizes BRCA1 in the repair of double-strand DNA breaks as part of the homologous recombination pathway.
Uncover Clues About Potential Germline Risk in Somatic Tumor Testing Reports
Approximately 10% of cancers are linked to a germline (inherited) pathogenic variant, which can be confirmed with germline susceptibility testing of a blood, skin, or saliva sample (not a tumor specimen). Identification of individuals with a germline pathogenic variant helps clinicians predict their risk for developing malignancies and provide recommendations for cancer prevention and early detection. If an individual develops a tumor, subsequent somatic predictive or prognostic biomarker tumor testing may be indicated. In some cases, a germline pathogenic variant may inform decisions about cancer-directed therapy, such as the use of a PARP inhibitor in those with a BRCA1 or BRCA2 pathogenic variant.
Learn How to Read a Somatic Biomarker Testing Report
Join ONS member Suzanne Mahon, RN, AOCN®, AGN-BC, FAAN, professor at Saint Louis University in Missouri and member of the St. Louis ONS Chapter, as she demonstrates how to examine and explore somatic biomarker testing reports. Understanding these reports is critical when providing patient education, and Mahon’s tips and tricks when identifying report components and their importance are helpful tools for oncology nurses to consider in their practice.
Genetic Disorder Reference Sheet: Neurofibromatosis Type 2
Neurofibromatosis type 2 is an autosomal dominant disorder characterized by bilateral vestibular schwannomas that can lead to significant hearing loss or deafness. Symptoms include tinnitus, hearing loss, and balance problems, with an average age of onset of 18–24 years and nearly 100% penetrance.
Genetic Disorder Reference Sheet: Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) is an autosomal dominant condition that stems from a pathogenic variant in the NF1 gene, which regulates the production of the tumor-suppressing neurofibromin protein. NF1 disorder is characterized by pigmentation changes (e.g., café au lait spots; see image), cutaneous neurofibromas, malignant nerve sheath tumors, gastrointestinal stromal tumors, and intellectual disorders. Signs and symptoms vary widely, but NF1 disorders occur in 1 in about 3,000–4,000 people. Almost half of the cases are de novo.
What Is MCED Testing?
Currently under study, multicancer early detection (MCED) tests have the potential to fill gaps in the screening process for some cancers, consequently leading to earlier diagnoses for cancers historically diagnosed at later stages because of a lack of screening options. MCED tests use various methods to detect multiple cancers from one blood sample, such as methylation-based assay, which analyzes methylation patterns in cell-free DNA. In cancer cells, hypermethylation may silence tumor suppressor genes in the early stages of cancer growth. DNA hypermethylation has become a promising biomarker for early cancer detection.
Learn How to Read a Germline Genomic Testing Report
Join ONS member Suzanne Mahon, RN, AOCN®, AGN-BC, FAAN, professor at Saint Louis University in Missouri and member of the St. Louis ONS Chapter, as she demonstrates how to examine and explore germline genomic testing reports. Understanding these reports is critical when providing patient education, and Mahon’s tips and tricks when identifying report components and their importance are helpful tools for oncology nurses to consider in their practice.
An Oncology Nurse’s Guide to Cascade Testing
A critical and often overlooked component of germline biomarker testing, cascade testing involves identifying biologic relatives at risk for inheriting a specific known family pathogenic variant after it’s first found in the family and extending the offer for germline biomarker testing to them.
Genetic Disorder Reference Sheet: FH Tumor Predisposition Syndrome
Fumarate hydratase deficiency occurs in individuals who have homozygous pathogenic variants in the tumor suppressor FH gene. The condition results in poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Development is severely delayed, and individuals are often nonverbal, unable to walk, and die in early childhood.
The Case of the Biomarker Database Discoveries
Macy is a 57-year-old patient with a history of hormone receptor–positive invasive ductal carcinoma of the right breast, diagnosed in 2017. She achieved complete remission after chemotherapy with anthracycline plus paclitaxel followed by bilateral mastectomy with reconstruction in 2018.
Genetic Disorder Reference Sheet: PTEN Hamartoma Tumor Syndrome
Alterations in the phosphatase and tensin (PTEN) homologue gene result in PTEN hamartoma tumor syndrome, which includes Cowden, Bannayan-Riley-Ruvalcaba, and PTEN-related Proteus and Proteus-like syndromes. Pathogenic variants in the PTEN gene are associated with increased risk for developing multiple benign and malignant tumors, some of which may occur in childhood.
NIH’s All of Us Research Program Starts Returning Genetic Health-Related Results to Participants
To help historically underrepresented communities learn more about their health, the National Institutes of Health’s All of Us Research Program began returning personalized health-related DNA results to more than 155,000 participants, NIH reported in December 2022. The reports include information on whether participants have an increased risk for certain health conditions and how they might process certain medications.
Direct-to-Consumer Genomic Testing in Patients With Cancer
Direct-to-consumer genomic testing is a patient-initiated type of testing that is marketed to the general public in advertisements on all media. The tests can be purchased online or in stores without requiring a healthcare professional order or third-party payer authorization. Customers send a saliva sample to the company and view their test results on a secure website, but the results are not included in their electronic health record unless they specifically request it.
Genetic Disorder Reference Sheet: BAP1
Isolated in 1998 as a tumor suppressor gene, BAP1 pathogenic variants have been identified in at least 200 families. More cases will be found as germline pathogenic variant testing becomes more readily available and routinely offered to patients with cancer.
Build Your Confidence in Next-Generation Sequencing With Nursing Toolkits and Resources
Essential biomarker testing technologies like next-generation sequencing are increasing our comprehension of cancer genetics and genomics. Biomarker testing results provide prognostic and predictive information about a tumor’s biology and growth to guide treatment decisions. Patients with cancer are turning to their oncology nurses to help them understand their complex test results and corresponding recommended treatment plans, yet many oncology nurses have minimal, if any, formal training in the area.
Genetic Disorder Reference Sheet: HOXB13
An altered HOXB13 gene may increase a patient’s risk for developing prostate cancer. The HOXB13 gene is expressed in the prostate beginning in early development and affects prostate cell proliferation and differentiation and androgen receptor regulation. When it acts as a tumor suppressor gene, HOXB13 codes for a protein that regulates cell division. However, altered copies of HOXB13 are inactivated, meaning that it does not function properly or does not produce the protein it codes for, resulting in uncontrolled cell division.
Genetic Counselors Help Patients and Oncology Nurses Predict Current and Future Cancer Diagnoses
Many of our patients are individuals who haven’t developed cancer but might have a concerning family history of the disease. We rely on healthcare providers like oncology nurses to identify individuals with concerning cancer histories and refer them to genetic counselors for a complete risk assessment, including genetic testing when appropriate, to determine their risk and recommend proactive measures to reduce it.
Understand Genomic Variants to Confidently Educate Your Patients
Nurses’ consistent and correct use of genomics terminology is critical to reduce confusion and provide safe genomics care to patients and their families, especially when explaining the meaning of genomic tests or findings.
Oncology Nurses’ Role in Translating Biomarker Testing Results
As oncology biomarker testing becomes a routine part of clinical practice, so does first-line use of their associated targeted therapies such as monoclonal antibodies, checkpoint inhibitors, and tyrosine kinase inhibitors.
Genetic Disorder Reference Sheet: Multiple Endocrine Neoplasia Type 2
Multiple endocrine neoplasia type 2 is an autosomal dominant disease that occurs because of germline pathogenic variants in the rearranged during transfection (RET) proto-oncogene. The RET gene was isolated in 1993 and pathogenic variants affect 1–10 per 100,000 people. Approximately 50% of cases are de novo.
Genetic Disorder Reference Sheet: Multiple Endocrine Neoplasia Type 1
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant genetic disease affecting about 1 in 30,000 people. Pathogenic variants in the MEN1 gene are associated with benign and malignant tumors in the parathyroid glands, pituitary gland, pancreas, duodenum, and stomach.
Minority Populations Represent Nearly Half of 100,000 Whole Genome Sequences for Researchers Through All of Us
Among the first set of nearly 100,000 whole genome sequences from participant partners in the National Institutes of Health’s (NIH) All of Us Research Program, “about half come from people who self-identify with a racial or ethnic minority group,” Joshua Denny, MD, MS, All of Us chief executive officer, and Lawrence Tabak, DDS, PhD, NIH acting director, said. “That’s extremely important because, until now, over 90% of participants in large genomic studies were of European descent. This lack of diversity has had huge impacts—deepening health disparities and hindering scientific discovery from fully benefiting everyone.”
Genetic Disorder Reference Sheet: Von Hippel-Lindau Syndrome
An inherited disorder characterized by the formation of benign and malignant tumors and cysts throughout the body, Von Hippel-Lindau syndrome (VHL) occurs with an altered VHL tumor suppressor gene with autosomal dominant transmission. Estimated incidence is 1 in 36,000 people, both males and females equally, and the mean age of onset is 26 years. About 20% of patients with VHL are the first person in their family to have the pathogenic variant (i.e., de novo). The diagnosis is made with germline biomarker testing.
FDA Approves Alpelisib for PIK3CA-Related Overgrowth Spectrum
On April 5, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to alpelisib (Vijoice®) for adult and pediatric patients aged two and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy.
The Oncology Nurse’s Role in Identifying Patients for Cancer Genetics Counseling
During personal and family medical history assessments, many patients report multiple cancer diagnoses in their family or concerns that other family members might be at increased risk for developing cancer. Patients and families might also ask their nurse about risk or parameters for genetic testing. Timely and appropriate referral to genetics professionals for counseling and possible testing for germline risk of malignancy enables individuals at increased risk to follow recommended surveillance and consider surgery and other preventive strategies, ultimately decreasing their risk of cancer-related morbidity and mortality.
Advocate for Equal Access for Next Generation Sequencing and Clinical Trials
Janice is an oncology nurse in a rural community cancer center. Only one of the three oncologists in the practice discusses clinical trials with their patients and typically not until after patients complete two to three lines of therapy. Also, the practice does not have a process for when to order next generation sequencing (NGS). Janice feels it is not ethical that the patients coming to the clinic do not have equal access to those important services.
Genetic Disorder Reference Sheet: PALB2
PALB2 refers to partner and localizer of BRCA2. The gene was isolated in 2007 and is the third most common gene associated with breast cancer risk. Both men and women are at increased risk for developing multiple cancers if they have a pathogenic PALB2 variant (see sidebar).
Never Smokers With Lung Cancer May Have One of Three Molecular Subtypes
Most lung cancers in patients who have no smoking history are the result of natural genetic variants in the body that can be classified into one of three molecular subtypes, researchers reported in study finding published in Nature Genetics.
Genetic Disorder Reference Sheet: CDH1 and Hereditary Diffuse Gastric Cancer
Pathogenic variants in the CDH1 gene are associated with hereditary diffuse gastric cancer (HDGC), a poorly differentiated adenocarcinoma that infiltrates into the stomach wall. It causes the stomach wall to thicken without forming a distinct mass, which limits effective screening strategies.
Help Patients Understand Biomarker Test Results and Clinical Trials Options
Many of today’s new drug approvals and standard-of-care treatments have a companion diagnostic test that identifies biomarkers in a patient’s tumor tissue or blood to determine whether they are an appropriate candidate for the therapy. When those results show that they’re not a good match for the U.S. Food and Drug Administration (FDA)-approved treatment, the findings may identify a biomarker-directed clinical trial as an alternative option. Here’s how oncology nurses can help patients understand which clinical trials listed on their test results might be an option for them.
Oncology Nursing Society Issues a Call to Action for Using Appropriate Genomics Terminology for Safety and Quality
The Oncology Nursing Society (ONS) is calling all oncology nurses to become fluent in the ONS Genomics Taxonomy terms and to use them in their practice. Using consistent and correct genomics terminology minimizes confusion and misconceptions and contributes to the high quality and safe delivery of cancer care.
New NIH Program Aims to Increase Gene Therapies for Rare Diseases
To accelerate the development of gene therapies for the 30 million Americans who have been diagnosed with a rare disease, in October 2021 the National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), 10 pharmaceutical companies, and five nonprofit organizations announced the creation of the Bespoke Gene Therapy Consortium (BGTC). The consortium is optimizing and streamlining the gene therapy development process to help fill the unmet medical needs of people with rare diseases.
Genetic Disorder Reference Sheet: Familial Adenomatous Polyposis
Individuals with 10–100+ polyps may have a germline pathogenic variant in the APC gene, placing them at higher risk for developing colorectal, gastrointestinal, and other cancers. The condition is known as familial adenosis polyposis (FAP), and loss of function in the APC gene is the first step in the adenoma-to-carcinoma sequence. Some people have an attenuated form (aFAP), with delayed polyp growth and fewer polyps (see sidebar). As many as 20% are de novo, meaning that they are the first in their family to have an identified pathogenic variant.
Genetic Counselors Help Patients and Providers Understand Biomarker Testing Goals and Results
Genetic counselors have a unique ability to explain complex genetic information to patients, providers, and our healthcare colleagues and to empower patients to take an active role in their healthcare decisions. We review biosignature data points and help explain the difference between variants that were acquired (somatic) versus those that may have a germline component, or possibly inherited from a parent. By working with oncology teams, genetic counselors provide guidance on potential next steps to evaluate variation occurrences and how providers, patients, and their families can use the information to guide their care.
Genetic Disorder Reference Sheet: ATM Pathogenic Variants
An estimated 1%–2% of adults have one pathogenic ataxia telangiectasia mutated (ATM) gene variant (heterozygous) and are considered carriers. People who are homozygous (two altered copies) have ataxia-telangiectasia (A-T), a hereditary condition that often appears in childhood and is characterized by progressive neurologic problems that lead to difficulty walking and an increased risk for developing various malignancies. Children with A-T may begin staggering and appear unsteady (ataxia) shortly after learning to walk.
NIH Provides $185 Million to Advance Understanding of Human Genome Functions
To drive the advancement of our understanding of the human genome, the National Institute of Health (NIH) is providing $185 million in funding over the next five years, the agency announced in September 2021.
This Is Why Red Meat Increases Colorectal Cancer Risk
Frequent red and processed meat consumption leaves a specific pattern of DNA damage in colorectal cells that contributes to the formation of tumors, researchers reported in study findings published in Cancer Discovery.
A Body of Evidence Helps Nurses Manage CAR T-Cell Therapy Toxicities
When chimeric antigen receptor (CAR) T-cell therapies were first approved for cancer in 2017, nurses didn’t have years of clinical practice experience with the treatment to understand its full scope of nursing implications yet. Now that nearly five years have passed—and new CAR T-cell therapies have been approved, bringing the total number of treatments to five as well—oncology nurses and nurse scientists have built a robust knowledge base.
Prognostic Biomarkers May Help Predict Rhabdomyosarcoma Outcomes
TP53 and MYOD1 variants are associated with more aggressive forms of rhabdomyosarcoma, a rare childhood cancer, and poorer outcomes, according to the results of the largest international genomic profiling study of the disease. The findings, which were published in the Journal of Clinical Oncology, have implications for somatic biomarker testing to guide tailored treatment approaches.
Whole-Genome Sequencing May Guide Treatment Choices for AML and MDS
When compared to conventional testing on the same samples from patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), whole-genome sequencing–based testing detected the same abnormalities—and new genetic information in about a quarter of patients, potentially changing treatment selection for more than half of those patients, researchers said in the New England Journal of Medicine.
New Form of CAR T Cells May Target Genetic Alteration Common to All Cancers
Scientists created a new cancer immunotherapy approach that uses a new type of CAR T cells to stimulate an immune response against cells that are missing one gene copy. They reported their findings in Proceedings of the National Academy of Sciences.
What Is CRISPR?
Clustered regularly interspaced short palindromic repeats (CRISPR) is a commonly seen term for readers of science news and literature across a variety of industries. But reading the word often doesn’t automatically translate to understanding it and its implications. Here’s what oncology nurses need to know about CRISPR.
Genetic Disorder Reference Sheet: MUTYH-Associated Polyposis
MUTYH-associated polyposis (MAP) is an autosomal recessive hereditary cancer syndrome. It’s most commonly seen in people of northern European ancestry, where an estimated 1 in 20,000–40,000 have MAP (two pathogenic variants on opposite chromosomes) and 1%–2% have one MUTYH pathogenic variant.
Genetic Disorder Reference Sheet: BRCA1 and BRCA2 Hereditary Cancers
BRCA1- or BRCA2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer. The prevalence of BRCA1 and BRCA2 pathogenic variants in the general population is estimated at 1 in 400–500 people, although it increases to 1 in 40 for those of Ashkenazi Jewish ancestry, which is linked to three founder pathogenic variants (BRCA1 c.68_69delAG, BRCA1c.5266dupC, and BRCA2 c.5946delT).
Genomics Test Guides Treatment Decisions for Prostate Cancer
The Decipher genomics test, which measures activity of 22 genes among seven known cancer pathways, independently estimates patients’ risk of prostate cancer metastasis, death, and overall survival and helps identify patients most likely to benefit from hormone therapy, researchers reported in study findings published in JAMA Oncology.
NHGRI Proposes Action Agenda for Building Diverse Genomics Workforce
Thanks to the National Institutes of Health’s National Human Genome Research Institute (NHGRI), cancer treatments and cures once out of reach are now closer than ever. So is our understanding about the human condition. As part of its latest strategic vision for the future of human genomics, NHGRI announced an action agenda to substantially enhance the industry’s workforce diversity by 2030.
The Case of the Targeted Therapy Toxicity
Tyrone is a 74-year-old man with a history of acute myeloid leukemia (AML), type 2 diabetes, and hypertension who was admitted to the hospital after lab results revealed 40% circulating blasts in his peripheral blood that was concerning for relapsed disease. He was diagnosed with AML three years ago and achieved remission after treatment with a hypomethylating agent.