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.”

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.

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.

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.

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.

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).

Analogies and visuals are powerful learning tools. If you’re one of the many nurses whose eyes glaze over when approaching genomics, consider connecting the “omics” concepts to interpretative visuals, clinical practice, and everyday life examples to enhance your learning and make the concepts more relevant to you. Here’s an example of how it can be done.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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). 

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.

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. 

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. 

The CHEK2 (checkpoint kinase 2) tumor suppressor gene provides cells with instructions for making a protein known as CHK2, which becomes active when the cell’s DNA is damaged or strands of it break. CHEK2 halts cell division and enables either cell repair or destruction. Without a properly functioning CHEK2 gene, cells lose a key restraint on their growth which may lead to uncontrolled cells and possibly malignancy. CHEK2*1100delC is the most common pathogenic variant and most prevalent in European populations.

Lynch syndrome, now referred to as hereditary nonpolyposis colorectal cancer (HNPCC), was first identified in a family in 1895. In 1966, Henry Lynch reported a series of families with colon and other cancers in the Nebraska area. Today, the evidence shows that HNPCC is associated with germline pathogenic variants in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes.

Patients with cancer who experience unexpected and long-lasting treatment outcomes are considered exceptional responders, but researchers and clinicians had no insight as to why the patients did so well with treatment. Results of a new study now show that genomic characterizations of cancer can uncover genetic alterations that may contribute to the phenomenon, researchers reported in Cancer Cell.

Turning on the body’s inflammasome with epigenetic therapy may improve the efficacy of PARP inhibitors across multiple tumor types, possibly expanding the therapy’s application to new cancers, researchers reported in Proceedings of the National Academy of Sciences.

Our understanding of cancer’s genetic components is constantly growing, with new cancer susceptibility genes discovered every year that change how we screen for and treat cancer. Genetics specialists keep up with the latest information and implications of genetic results is and can be a great addition to comprehensive oncology teams.

Since the mapping of the human genome in 2003, genetic testing has rapidly evolved from single-gene tests to more complex profiles that measure multiple genes; it’s now part of standard care for many cancer types. Precision oncology allows clinicians to take patient-specific genomic factors into consideration when making treatment decisions, which can lead to improved outcomes, lower overall cost, and fewer side effects.

Cancer genomics influences all oncology nursing roles. Walking through the cancer care continuum shows how genomics—and oncology nursing—are involved at every level.

The Oncology Nursing Society (ONS) launched its inaugural ONS Hackathon™ on November 9, 2020, a competition designed to identify innovative ways to address challenging issues in the delivery of quality cancer care. Meghan O. Coleman, DNP, CRNP, and Alison McDaniel, BSN, RN, OCN^®’s winning project, Evidence-Based Quality Understanding in Pathology, provided ways to solve the problem of unequal access to biomarker and other genetic and genomic testing.

Approximately 700 members responded to ONS’s 2020 genomics survey, which gauged oncology nurses’ current genomic knowledge, applications in practice, and the specific questions they have about genetics and genomics. Here are the answers to the most frequently asked questions based on the survey responses.

In the United States, breast cancer is the most commonly diagnosed cancer in women. One in eight women will develop invasive disease in their lifetime with approximately 270,00 new cases diagnosed in the United States in 2019. Caucasian women have the highest incidence rate, whereas African American women are most likely to die from the disease. The five-year survival rate is 91%, with an estimated 3.8 million breast cancer survivors living in the United States.

The Human Genome Project determined the DNA sequence (order of base pairs) of the entire human genome. Humans are 99.9% identical at the level of base pair ordering, but the 0.1% difference contributes to disease risk. Upon completion of the human genetic blueprint, research turned to identifying and cataloguing genomic variation as well as determining the clinical relevance of variants.

On September 4, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pralsetinib (Gavreto™) for adult patients with metastatic, RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.

Patients who watch crime shows think that DNA testing is as simple as taking a cheek swab and getting the results in two minutes so the case is solved at the end of the 42-minute episode. The reality? DNA can be identified from buccal cells in a cheek swab, but results take several weeks to obtain and are not always a simple negative or positive.

Patients approach genetic testing, either for germline (inherited) or somatic (tumor) alterations, hoping it will provide valuable information about their cancer risk, prognosis, or treatment options. Next-generation sequencing makes it possible to test for panels of 40 or more genes simultaneously. By testing more genes, the possibility of finding an actionable, informative result improves, but so does the chance of having a result with one or more variants of unknown clinical significance.

With the massive paradigm shift in cancer therapy to precision medicine, the use of biomarkers and biomarker testing has also rapidly evolved to guide treatment selection. However, the terminology used in genomics is complex and inconsistent, and patient advocacy organizations recommend using a common taxonomy to prevent confusion among patients and providers alike. Nurses spend more time with patients and families than any other member of the healthcare team and can reinforce common language and terminology. As a nurse, here are the terms you need to understand.

Genetics testing is not just about one family member; the results have implications for an entire family. Results of genetic testing can be confusing, and families often need assistance understanding what it means for them. Genetics counseling before and after testing is very important to help individuals and families understand the results of genetic testing when they are received and over time. 

When referring patients for genetics counseling and possible testing for hereditary risk, oncology nurses can help relieve their trepidation and anxiety by explaining what to expect during the visit. See the sidebar for key indications for referral.

Further understanding of the human genome and the proliferation of genetic data has spurred significant advancement in the understanding of the way cancer impacts individuals. To share the crucial work in genetics, the National Institutes of Health (NIH), led by the National Institute for Cancer (NCI), has compiled survivor stories from patients who have benefited from cutting-edge genomic technology. Their stories illustrate and contribute to the ongoing successes brought on by NIH’s genomic efforts.

Although most cancers contain four to five driver mutations, those drivers remain unknown for about 5% of cancers, according to results of a series of studies examining genomes from 38 different cancer types. The international Pan-Cancer Analysis of Whole Genomes Consortium reported the findings in a collection of 23 articles published in Nature and other affiliated journals.

Genomic testing identifies germline or inherited DNA changes that increase a person’s cancer risk, and it also can identify or profile the somatic or acquired changes in a tumor that guide selection of appropriate targeted therapies. The latter type of genomic testing is an analysis of DNA sequence information.

Cancer occurs from pathogenic genetic variants (formerly referred to as mutations) that involve changes in the order of the base pairs, including substitutions, deletions, additions, or shifts. Pathogenic variants can be divided into two broad categories based on the tissue from which they originate.

According to findings from a new analysis published in JAMA Oncology, multigene testing should be expanded to all women with breast cancer and not just those with certain family histories or clinical factors.