Nearly 100,000 patients submitted saliva samples to a genetic testing laboratory, providing insights into their disease risk
Researchers at Mayo Clinic have employed next-generation sequencing technology to produce a massive collection of exome data from more than 100,000 patients, offering a detailed look at genetic variants that predispose people to certain diseases. The study, known as Tapestry, was administered by doctors and scientists from the clinic’s Center for Individualized Medicine and produced the “largest-ever collection of exome data, which include genes that code for proteins—key to understanding health and disease,” according to a Mayo Clinic news release.
For our clinical laboratory professionals, this shows the keen interest that a substantial portion of the population has in using their personal genetic data to help physicians identify their risk for many diseases and types of cancer. This support by healthcare consumers is a sign that labs should be devoting attention and resources to providing these types of gene sequencing services.
As Mayo explained in the news release, the exome includes nearly 20,000 genes that code for proteins. The researchers used the dataset to analyze genes associated with higher risk of heart disease and stroke along with several types of cancer. They noted that the data, which is now available to other researchers, will likely provide insights into other diseases as well, the news release notes.
“What we’ve accomplished with the Tapestry study is a blueprint for future endeavors in medical science,” said gastroenterologist and lead researcher Konstantinos Lazaridis, MD (above), in the news story. “It demonstrates that through innovation, determination and collaboration, we can deeply advance our understanding of DNA function and eventually other bio-molecules like RNA, proteins and metabolites, turning them into novel diagnostic tools to improve health, prevent illness, and even treat disease.” Some of these newly identified genetic markers may be incorporated into new clinical laboratory assays. (Photo copyright: Mayo Clinic.)
How Mayo Conducted the Tapestry Study
One notable aspect of the study was its methodology. The study launched in July 2020 during the COVID-19 pandemic. Since many patients were quarantined, researchers conducted the study remotely, without the need for the patients to visit a Mayo facility. It ran for five years through May 31, 2024. The news release notes that it’s the largest decentralized clinical trial ever conducted by the Mayo Clinic.
The researchers identified 1.3 million patients from the main Mayo Clinic campuses in Minnesota, Arizona, and Florida who met the following eligibility criteria:
Participants had to be 18 or older,
they had to have internet and email access, and
be sufficiently proficient in speaking and reading English.
More than 114,000 patients consented to participate, but some later withdrew, resulting in a final sample of 98,222 individuals. Approximately two-thirds were women. Mean age was 57 (61.9 for men and 54.3 for women).
“It was a tremendous effort,” said Mayo Clinic gastroenterologist and lead researcher Konstantinos Lazaridis, MD, in the news release. “The engagement of such a number of participants in a relatively short time and during a pandemic showcased the trust and the dedication not only of our team but also of our patients.”
He added that the researchers “learned valuable lessons about some patients’ decisions not to participate in Tapestry, which will be the focus of future publications.”
Three Specific Genes
Enrolled patients were invited to visit a website, where they could view a video and submit an eligibility form. Once approved, they completed a digital consent agreement and received a saliva collection kit. Participants were also invited to provide information about their family history.
Helix, a clinical laboratory company headquartered in San Mateo, Calif., performed the exome sequencing.
Though Helix performed whole exome sequencing, the researchers were most interested in three specific sets of genes:
Patients received clinical results directly from Helix along with information about their ancestry. Clinical results were also transmitted to Mayo Clinic for inclusion in patients’ electronic health records (EHRs).
Among the participants, approximately 1,800 (1.9%) had what the researchers described as “actionable pathogenic or likely pathogenic variants.” About half of these were BRCA1/2.
These patients were invited to speak with a genetic counselor and encouraged to undergo additional testing to confirm the variants.
Tapestry Genomic Registry
In addition to the impact on the participants, Mayo Clinic’s now has an enormous amount of raw sequencing data stored in the Tapestry Genomic Registry, where it will be available for future research.
The database “has become a valuable resource for Mayo’s scientific community, with 118 research requests submitted,” the researchers wrote in the news release. Mayo has distribution more than a million exome datasets to other genetic researchers.
“What we’ve accomplished with the Tapestry study is a blueprint for future endeavors in medical science,” Lazaridis noted. “It demonstrates that through innovation, determination, and collaboration, we can deeply advance our understanding of DNA function and eventually other bio-molecules like RNA, proteins and metabolites, turning them into novel diagnostic tools to improve health, prevent illness, and even treat disease.”
Everything about this project is consistent with precision medicine, and the number of individuals discovered to have risk of cancers is relevant. Clinical laboratory professionals understand these ratios and the importance of early detection and early intervention.
Half of the people tested were unaware of their genetic risk for contracting the disease
Existing clinical laboratory genetic screening guidelines may be inadequate when it comes to finding people at risk of hereditary breast-ovarian cancer syndromes and Lynch syndrome (aka, hereditary nonpolyposis colorectal cancer). That’s according to a study conducted at the Mayo Clinic in Rochester, Minn., which found that about half of the study participants were unaware of their genetic predisposition to the diseases.
Mayo found that 550 people who participated in the study (1.24%) were “carriers of the hereditary mutations.” The researchers also determined that half of those people were unaware they had a genetic risk of cancer, and 40% did not meet genetic testing guidelines, according to a Mayo Clinic news story.
The discoveries were made following exome sequencing, which the Mayo Clinic news story described as the “protein-coding regions of genes” and the sites for most disease-causing mutations.
“Early detection of genetic markers for these conditions can lead to proactive screenings and targeted therapies, potentially saving lives of people and their family members,” said lead author Niloy Jewel Samadder, MD, gastroenterologist and cancer geneticist at Mayo Clinic’s Center for Individualized Medicine and Comprehensive Cancer Center.
“This study is a wake-up call, showing us that current national guidelines for genetic screenings are missing too many people at high risk of cancer,” said lead author Niloy Jewel Samadder, MD (above), gastroenterologist and cancer geneticist at Mayo Clinic’s Center for Individualized Medicine and Comprehensive Cancer Center. New screening guidelines may increase the role of clinical laboratories in helping physicians identify patients at risk of certain hereditary cancers. (Photo copyright: Mayo Clinic.)
Advancing Personalized Medicine
“The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify carriers of HBOC (hereditary breast and ovarian cancer) and LS (Lynch syndrome),” the authors wrote in JCO Precision Oncology.
For the current study, Helix, a San Mateo, Calif. population genomics company, collaborated with Mayo Clinic to perform exome sequencing on the following genes:
BRCA1 and BRCA2 genes (hereditary breast and ovarian cancer).
Mayo/Helix researchers performed genetic screenings on more than 44,000 study participants. According to their published study, of the 550 people who were found to have hereditary breast cancer or Lynch syndrome:
387 had hereditary breast and ovarian cancer (27.2% BRCA1, 42.8% BRCA2).
163 had lynch syndrome (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2, and 0.2% EPCAM).
Participants recruited by researchers hailed from Rochester, Minn.; Phoenix, Ariz.; and Jacksonville, Fla.
Minorities were less likely to meet the NCCN criteria than those who reported as White (51.5% as compared to 37.5%).
“Our results emphasize the importance of expanding genetic screening to identify people at risk for these cancer predisposition syndromes,” Samadder said.
Exome Data in EHRs
Exomes of more than 100,000 Mayo Clinic patients have been sequenced and the results are being included in the patients’ electronic health records (EHR) as part of the Tapestry project. This gives clinicians access to patient information in the EHRs so that the right tests can be ordered at the right time, Mayo Clinic noted in its article.
“Embedding genomic data into the patient’s chart in a way that is easy to locate and access will assist doctors in making important decisions and advance the future of genomically informed medicine.” said Cherisse Marcou, PhD, co-director and vice chair of information technology and bioinformatics in Mayo’s Clinical Genomics laboratory.
While more research is needed, Mayo Clinic’s accomplishments suggest advancements in gene sequencing and technologies are making way for data-driven tools to aid physicians.
As the cost of gene sequencing continue to fall due to improvement in the technologies, more screenings for health risk factors in individuals will likely become economically feasible. This may increase the role medical laboratories play in helping doctors use exomes and whole genome sequencing to screen patients for risk of specific cancers and health conditions.
Findings could lead to new clinical laboratory cancer screening tests for BRCA1 and BRCA2 among specific population regions
Descendants of a remote Scottish island are much more likely to carry a cancer-causing BRCA2 gene than the rest of the UK. That’s according to a study conducted by the University of Edinburgh in Scotland. For pathologists and clinical laboratory managers, the study’s findings demonstrate how ongoing research into the genetic makeup of subpopulations will find groups that have higher risk for specific health conditions than the general population. Thus, diagnosticians can pay closer attention to screening these groups to achieve early diagnosis and intervention.
“The findings follow earlier research from the Viking Genes study that found a cancer-causing variant in the related BRCA1 gene, common among people from Orkney [a group of islands off Scotland’s northern coast],” noted a University of Edinburgh news release.
In their latest research, the genetic scientists discovered that the BRCA2 gene can be found in one in every 40 people with heritage from the island of Whalsay in Scotland’s Shetland island group. This gene is one of the most common genes that can be linked to breast cancer and ovarian cancer in women and breast and prostate cancer in men.
Those who inherit the BRCA2 gene have a significantly higher risk of developing certain cancers than the general population. For example, according to the National Cancer Institute, more than 60% of women who inherit the gene will develop breast cancer in their lifetimes.
The volunteers in the Viking Genes study have a risk of having a BRCA2 gene that is 130 times higher than the general UK population. According to the BBC, geneticists believe the gene can be traced back to one family from the island of Whalsay before 1750.
“It is very important to understand that just two gene changes account for more than 90% of the inherited cancer risk from BRCA variants in Orkney and Shetland. This is in stark contrast to the situation in the general UK population, where 369 variants would need to be tested to account for the same proportion of cancer risk from BRCA genes. Any future screening program for the Northern Isles should therefore be very cost-effective,” said James Wilson, DPhil, FRCPE (above), Professor of Human Genetics at University of Edinburgh and leader of the study, in a news release. Clinical laboratories in the UK will be involved in those screenings. (Photo copyright: Scottish Genomes Partnership.)
Early Diagnosis Brings Hope to Families
The UK’s National Health Service (NHS) offers genetic testing to relatives of people with a known BRCA variant. Individuals with at least one Whalsay grandparent, and who have a close family history of breast, ovarian, or prostate cancer, can also request NHS testing.
As the BBC reported, University of Edinburgh’s discovery has given families answers and hope for the future. Individuals who fit the criteria for being at risk of inheriting the BRCA gene can narrow their testing and work more specifically on preventative measures with their doctors.
Christine Glaser, a woman from Lerwick in Shetland, learned she carried the BRCA gene after participating in the study. Though the Viking genes research took place nearly a decade ago, scientific understanding of genes has improved allowing geneticists to draw new conclusions from previous studies.
Although Glaser lost her sister to ovarian cancer, she and her family were unaware of their heightened genetic risk.
“I got offered preventative measures so I could get my ovaries removed and I could get a mastectomy. So, that’s what I did … when I got my ovaries removed, they checked them and there was no cancer, but then I had a mammogram and they found cancer,” she told the BBC. Glaser’s cancer was successfully treated thanks to early detection.
Closing Gap in Genetic Testing
“This BRCA2 variant in Whalsay I think arose prior to 1750. This is why these things become so common in given places because many people descend from a couple quite far back in the past, and if they have a cancer variant, then a significant number of people today—five or even 10 generations later—will have it. This is true everywhere in Scotland, it’s just magnified in these small places,” said James Wilson, DPhil, FRCPE, Professor of Human Genetics at University of Edinburgh, who led the study on Viking genes that found individuals with familial ties to two small Scottish communities may be at a higher risk of having a cancer-causing gene.
Wilson hopes to see testing for these genetic abnormalities become more common for these at-risk communities.
“The Ashkenazi Jewish community have BRCA1 and BRCA2 variants that also have a frequency of about one in 40,” he told the BBC. “The Ashkenazi Jewish population in England are able to take part in genetic testing for these genes but that’s not yet the case in Scotland.”
The findings of the most recent University of Edinburgh genetic study are very new. Future developments and offerings from the NHS may be influenced by the results.
Deeper understanding about the genetic make-up of certain population subgroups could lead to new genetic personalized medicine and preventative testing for those at risk of hereditary cancer. In turn, it could also encourage individuals to seek preventative care earlier. Thus, pathologists and clinical laboratory managers should keep an eye on these developments and be prepared to work with geneticists who may develop new screening methods for BRCA1 and BRCA2.
Ongoing increases in the global number of prostate cancer cases expected to motivate test developers to deliver better screening tests to pathologists and clinical lab scientists
No less an authority than the peer-reviewed healthcare journal The Lancet is drawing attention to predictions of increasing prostate cancer cases across the globe, triggering calls for the development of cheaper, faster, and more accurate assays that pathologists and medical laboratories can use to screen for—and diagnose—prostate cancer.
Swift population growth and rising life expectancy will cause the prostate cancer death rate to nearly double in the next 20 years, according to a new study that has led scientists to call for immediate, critical improvements in clinical laboratory testing for cancer screening, Financial Times (FT) reported.
“Low- and middle-income countries need to prepare to prevent a sharp rise in fatalities while richer nations should pay more attention to young men at higher risk of the disease,” FT noted. The study, titled, “The Lancet Commission on Prostate Cancer: Planning for the Surge in Cases,” predicts cases will jump from 1.4 million in 2020 to 2.9 million by 2040.
“Prostate cancer is the most common cancer in men in 112 countries, and accounts for 15% of cancers. In this Commission, we report projections of prostate cancer cases in 2040 on the basis of data for demographic changes worldwide and rising life expectancy. … This surge in cases cannot be prevented by lifestyle changes or public health interventions alone, and governments need to prepare strategies to deal with it,” the study authors wrote.
“The findings in this Commission provide a pathway forward for healthcare providers and funders, public health bodies, research funders, governments, and the broader patient and clinical community,” the authors noted. In their Lancet paper, the researchers define clear areas for improvement.
Given the shortage worldwide of pathologists—especially highly-trained pathologists—the gap between the demand/need for expanded prostate cancer testing as screens (along with prostate biopsies) and the available supply of pathologists will encourage companies to develop screening and diagnostic tests that are accurate and automated, thus increasing the productivity of the available pathologists.
“As more and more men around the world live to middle and old age, there will be an inevitable rise in the number of prostate cancer cases. We know this surge in cases is coming, so we need to start planning and take action now,” said Nick James, PhD (above), Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research, in a press release. Pathologists and medical laboratories worldwide will want to monitor progress of The Lancet Commission’s recommendations. (Photo copyright: Institute of Cancer Research.)
“Evidence-based interventions, such as improved early detection and education programs, will help to save lives and prevent ill health from prostate cancer in the years to come. This is especially true for low- and middle-income countries (LMICs) which will bear the overwhelming brunt of future cases,” he said in a press release.
Communication is key. “Improved outreach programs are needed to better inform people of the key signs to look out for and what to do next,” James N’Dow, MD, Professor and Chair in Surgery and Director of the Academic Urology Unit at the University of Aberdeen in the UK, told the Financial Times. “Implementing these in tandem with investments in cost-effective early diagnostic systems will be key to preventing deaths,” he added.
Capitalizing on artificial intelligence (AI) analysis to help translate results was another area The Lancet Commission researchers focused on, Financial Times noted.
AI could “subdivide disease into potentially valuable additional subgroups to help with treatment selection. In environments with few or no pathologists, these changes could be transformational,” the study authors wrote.
High Income Countries (HICs) would benefit from AI by empowering patients. “Linking cloud-based records to artificial intelligence systems could allow access to context-sensitive, up-to-date advice for both patients and health professionals, and could be used to drive evidence-based change in all settings,” the study authors added. Such a trend could lead to specialist prostate cancer pathologists being referred cases from around the world as digital pathology systems become faster and less expensive.
Effective treatment strategies and bolstering areas of need is also key, the study notes. “Many LMICs have urgent need for expansion of radiotherapy and surgery services,” the study authors wrote. The researchers stress the need to immediately implement expansion programs to keep up with anticipated near-future demand.
Cancer drug therapy should follow suit.
“Research and the development of risk-stratified regulatory models need to be facilitated,” the study authors noted, citing a focus on drug repurposing and dose de-escalation. “Novel clinical trial designs, such as multi-arm platforms, should be supported and expanded,” they added.
Unique Needs of LMICs, HICs
The Lancet Commission researchers’ recommendations shift depending on the financial health of a specific area. HICs are experiencing a 30-year decline in the number of deaths resulting from prostate cancer, presumably from additional testing measures and public health campaigns that may be lacking in LMICs, Financial Times reported. And as population growth soars, low-to-middle income populations “will need to be prepared for the strain the expected surge in cases will put on health resources.”
For HICs, the study dissected the limitations of prostate-specific antigen (PSA) testing. The researchers pointed out that PSA’s inaccuracies in screening symptomless patients can pinpoint “cancers that may never cause symptoms and need no treatment,” Financial Times reported.
Missing high-risk cases was also a cause for concern. “Diagnostic pathways should be modified to facilitate early detection of prostate cancer while avoiding overdiagnosis and overtreatment of trivial disease,” the study notes.
Screenings for high-risk younger men, and continuing public campaigns about prostate cancer, should be a focus for HICs, the study authors noted. “These would include people who have a family history of the disease, are of African ancestry, or carry a genetic mutation known as BRCA2,” Financial Times reported.
While the undertaking may sound intimidating—there is already such a heavy impact worldwide from prostate cancer—the researchers are optimistic of their recommendations.
“Options to improve care are already available at moderate cost. We found that late diagnosis is widespread worldwide, but especially in LMICs, where it is the norm. Early diagnosis improves prognosis and outcomes, and reduces societal and individual costs, and we recommend changes to the diagnostic pathway that can be immediately implemented,” the study authors wrote.
What Comes Next
“More research is needed among various ethnic groups to expand understanding of prostate cancer beyond the findings from studies that were largely based on data from white men,” The Lancet Commission told the Financial Times.
Astute pathologists and medical laboratories will want to monitor efforts to develop assays that are inexpensive, more accurate, and produce faster answers. Demand for these tests will be substantial—both in developed and developing nations.
Wait times blamed on the Irish National Health System’s ‘overstretched’ services and ‘under-resourced’ commitment to cancer genetic testing done by medical laboratories
Histopathologists in the UK and anatomic pathologists in the US understand the important role predictive genetic testing can play in helping patients understand their risk for certain types of breast, bowel, and ovarian cancers. While timely access to cancer testing may be routine in the United States, a report out of Ireland reveals patients in that country’s government-run healthcare system may have to wait up to two years or more for genetic counseling and testing.
UK Patients in Need of Genetic Services Are Switching from Public to Private Healthcare
While early access to genetic testing can provide opportunities for preventative treatments or earlier diagnosis of cancer, many patients in Ireland with a family history of cancer must wait months or years for genetic services. UCC Nursing Professor and Physiologist Josephine Hegarty, PhD, lead author of the ICS report, stated in a news release that “public cancer genetic services are overstretched. Waiting lists exist at every point on the pathway for people who need genetic services.”
She added, “Many patients spoken to seemed to abandon the waiting for overstretched public services in favor of paying for private testing and treatment.”
While the ICS report’s survey sample size was small—154 patients, family members, or members of the public—the data revealed:
One in seven respondents waited 13-24 months and one in 27 waited over 24 months for counseling and testing appointments.
Many people had changed from the public health system to private healthcare to speed up access to genetic testing.
The cumulative waiting time from referral to counseling, testing, receipt of genetic test results, and onwards to screening, surveillance, or prophylactic treatments [aka, preventive healthcare] can be up to four years, which patients see as time lost in terms of cancer prevention and early intervention.
Barriers to Genetic Services Affect Treatment Decisions
A separate survey of 52 healthcare professionals highlighted barriers for accessing services with six in 10 respondents saying they are under-resourced and four in 10 concerned about access to follow-up surgery for patients deemed to be at high risk.
In the ICS news release, breast cancer patient Margaret Cuddigan said genetic testing was not available to her at diagnosis.
“In those 13 months waiting for a result, I went through chemotherapy, a lumpectomy, and radiotherapy on my breast, only for a double mastectomy to be required once the BRCA mutation was known. Had I known this earlier, my course of treatment could have been very different,” Cuddigan said.
“I had to postpone a radiation treatment to go up to Dublin from Cork to do the genetic test, as it would have taken up to another 12 months in Cork, and then I waited over four months for the results. Once I received the news of the gene mutation, I had to navigate a path of risk-reducing surgeries,” she noted, adding, “I researched and sought out a surgeon myself.”
Long Waits for Genetic Testing Are Common in Single-Payer Healthcare
The waiting list for genetic cancer testing has long been an issue in Ireland. A 2017 article in the Irish Examiner, titled, “Woman Faces 18-month Wait for Vital Cancer Test,” brought to light the 18-month waiting time for BRCA1 and BRCA2 mutation testing for breast cancer. While the COVID-19 pandemic has further exacerbated the backlog of cancer treatment services, such issues are not new in single-payer healthcare systems.
Across the Irish Sea in Great Britain, some patients have experienced delays of six months before getting cancer test results. In “Shortage of Histopathologists in the United Kingdom Now Contributing to Record-Long Cancer-Treatment Waiting Times in England,” Dark Daily reported how prolonged wait times for cancer test results in the United Kingdom’s National Health Service are one disadvantage of a government-run, single-payer health system. With limited funds, frequently the government health program under invests in certain clinical services. It is not until several years later that the underinvestment reveals itself in the form of lengthy wait times.
Meanwhile, it is cancer patients and their families who pay the price for underinvestment because delays in their cancer test results then delay timely treatment decisions. This is particularly true when an immediate start of therapy for an aggressive form of cancer is imperative.
ICS Executive Director, Advocacy and External Relations, Rachel Morrogh, argues the solution is prioritizing cancer prevention within the Health Service Executive, which runs Ireland’s national healthcare system.
“The reality is the focus must be on urgent care, but we’re missing chances to keep people healthy (through genetic testing),” Morrogh told the Irish Independent. “We can prevent four in 10 cancers, but we have to prioritize prevention. There needs to be a significant investment and the expansion of capacity across all the follow-on services that someone with a genetic risk of cancer may need, focusing on the development of a dedicated and resourced pathway for them.
Irish Cancer Society’s Director of Advocacy and External Affairs Rachel Morrogh (above left with Donal Buggy, Director of Services, Delivery and Innovation at ICS) maintains that “Patients [in the Irish healthcare system] need a dedicated group of multi-disciplinary doctors following them so that they can be offered options and psycho-oncology support when they need it.” She added, “The government must now listen to patients and those working in our hospitals and provide more resourcing and staffing.” (Photo copyright: Irish Examiner.)
The ICS report found that limited access to timely genetically-guided health and oncology services is the result of multiple barriers to care.
“It is apparent from engaging directly with service users that waiting lists exist at every point on the pathway for people who need genetic [cancer testing] services,” the report states. “For those who may have a genetic risk of cancer, the wait times for access to [genetic cancer] testing alone (before counselling treatment, prophylactic surgery, etc.) can be up to two years. Barriers to accessing cancer genetic services include costs of tests, long processing time for referrals to tests, restrictive referral criteria, and difficulty in accessing information on cancer genetic services.”
In the forward she wrote for the ICS report, ICS Chief Executive Officer Averil Power said her organization would continue its push for improved access to genetic testing services. “Government needs to not only expand capacity for testing and counselling, but also ensure that the follow-on services that are needed by people diagnosed with a genetic risk of cancer are in place and can be accessed swiftly.”
The ICS report is another reminder to histopathologists in the UK—as well as anatomic pathologists in the US—that a single-payer healthcare system comes with its own flaws and access-to-care issues.
