News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups
Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups
Hosted by Robert Michel
Sign In

Mayo Clinic Researchers Uses Exome Sequencing to Identify Individuals at Risk of Hereditary Cancer

Nov 22, 2024 | Laboratory News, Laboratory Pathology, Laboratory Resources, Laboratory Testing, Molecular Diagnostics, Genetic Testing, Whole Gene Sequencing

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.

The Mayo researchers published their findings in the journal JCO Precision Oncology titled, “Exome Sequencing Identifies Carriers of the Autosomal Dominant Cancer Predisposition Disorders Beyond Current Practice Guideline Recommendations.”

“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.

Their work was a project of the Mayo Clinic Center for Individualized Medicine Tapestry study, which aims at advancing personalized medicine and developing a dataset for genetic research.

For the current study, Helix, a San Mateo, Calif. population genomics company, collaborated with Mayo Clinic to perform exome sequencing on the following genes:

According to the Mayo Clinic:

  • BRCA1 can lead to a 50% chance of breast cancer, and a 40% chance of ovarian cancer, respectively, as well as other cancers.
  • BRCA2 mutations suggest risk of breast cancer and ovarian cancer is 50% and 20%, respectively.
  • Lynch syndrome relates to an 80% lifetime risk of developing colorectal cancer and 50% risk of uterine and endometrial 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).
  • 52.1% were newly diagnosed carriers.
  • 39.2% of the 550 carriers did not meet genetic evaluation criteria set by the National Comprehensive Cancer Network (NCCN).
  • 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.

—Donna Marie Pocius

Related Information:

Exome Sequencing Identifies Carriers of the Autosomal Dominant Cancer Predisposition Disorders Beyond Current Practice Guideline Recommendation

Mayo Clinic Uncovers Genetic Cancer Risk in 550 Patients

Mayo Clinic’s Data-Driven Quest to Advance Individualized Medicine

Genome Sequencing of Tumors Are Helping Pathologist and Physicians Identify Useful Therapies for Patients with Unresponsive Cancers

Nov 2, 2015 | Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Pathology

Early research projects to sequence tumors in clinical settings are helping physicians and pathologists identify mutations that respond to specific therapeutic drugs

Step by step, progress is happening in the use of genome sequencing to advance personalized and precision medicine, with clinical laboratories and pathologists in the forefront of these developments. Much of this effort is focused on cancer and the sequencing of tumors.

One recent example comes from New York City, where the genomes of tumors of patients with unresponsive cancers were sequenced at the Institute for Precision Medicine at Weill Cornell and New York-Presbyterian Hospital Weill Cornell Medical Center. The outcomes of this effort demonstrates how the results of such testing can help patients who had not found an effective therapy to control their cancers. (more…)

Studies Show How Clinical Whole-Exome Sequencing May Forever Change the Future Practice of Medicine while Giving Pathologists a New Opportunity to Deliver Value

Apr 17, 2015 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory Pathology, Laboratory Testing

Similar study of exome sequencing at UCLA produces findings that mirror the diagnostic outcomes produced by researchers at the three Houston organizations

In recent years, pathologists and other clinical laboratory professionals have seen increasing evidence of the benefits of using exome sequencing for clinical diagnostic purposes.

Confirming their initial published findings of a 25% molecular diagnostic rate, researchers from Baylor College of Medicine (BCM), Baylor Human Genome Center, and the University of Texas Health Science Center at Houston have released results of a large sampling of 2,000 consecutive patients.

In this expanded study, published in the November 12, 2014, issue of the Journal of the American Medical Association (JAMA), 504 patients (25.2%) received a molecular diagnosis and 92 patients (4.6%) benefitted from medical intervention to ameliorate or eliminate negative symptoms. (more…)

Thomas Jefferson University Study Finds Critical Weakness in Commercially Manufactured Exome-Capture Test Kits Used by Some Medical Laboratories

Aug 22, 2014 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing

The four exome test kits examined as part of this study failed to deliver quality results, particularly because they often missed some disease-causing mutations altogether

Human exome sequencing is gaining favor among medical laboratories wanting to use this information for clinical purposes. However, the accuracy of some exome-capture test kits available on the market today has come under question.

A team from the Thomas Jefferson University in Philadelphia surveyed the potential false-negative rate of mutations in 56 disease-causing genes produced by four different commercially available human exome-capture test kits. The researchers found that these test kits failed to deliver quality results, sometimes missing mutations altogether, noted a report published by Medical Daily. (more…)

Study at University of Chicago Uses Supercomputer to Shorten Time Required to Analyze Whole Human Genome Sequences; May Help Pathologists Deliver Faster Diagnoses

Jun 4, 2014 | Digital Pathology, Instruments & Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations

Achievement at University of Chicago may help clinical laboratories analyze large quantities of genomic data much faster than ever before, thus shortening the time required to produce a diagnostic result

It’s a breakthrough in the time required to analyze data from whole human genome sequencing. Researchers at the University of Chicago have successfully demonstrated that genome analysis can be radically accelerated.

This could be a big deal for pathologists and clinical laboratory scientists. That’s because a faster time-to-answer from gene sequencing would increase its diagnostic and therapeutic value to clinicians.

Faster and more accurate analysis of genomic data holds the promise of advances in patient management and greater understanding of the genetic causes of risk and disease. This could mean expanded opportunities for pathologists to engage with clinicians in the use of genomic data to inform diagnosis, choice of treatment, and disease management. (more…)

;