MayoComplete next-generation sequencing: Transforming comprehensive cancer care

Eye on Innovation

In a world of ever-faster technical change, Mayo Clinic Laboratories is uniquely positioned to innovate. Collaboration with clinicians pinpoints unmet patient needs and facilitates the development of diagnostic testing that provides answers.

For patients facing a cancer journey, navigating diagnosis and treatment can be extremely

daunting. Fear of the unknown is compounded by a confusing ocean of emerging information on discoveries and technological advancements.

While each wave of progress brings about new types of treatment, including targeted and immune therapies linked to improved outcomes, the cancer’s nuances must be understood for these pioneering treatments to work.

Laboratory testing offers crucial information to help patients traverse the shifting landscape of therapeutic options. But not all tests are created equal. And not all results provide the clarity on which to base critical decisions.

Mayo Clinic Laboratories’ newly released suite of MayoComplete hematology and oncology next-generation sequencing (NGS) panels delivers precision answers on the genetic associations of an individual’s cancer. Results from MayoComplete NGS, which evaluates for gene mutations, rearrangements, and amplifications, deepen understanding of the specific disease process to facilitate individualized treatment selection.

“Tests like these assure patients get the best cancer care, as clinicians use these results to determine the best treatment strategies based on the patient’s tumor profile,” says Benjamin Kipp, Ph.D., chair of the Division of Laboratory Genetics and Genomics. “It's really that simple. The number of therapies available are increasing and they are improving outcomes, so we want to make sure our patients receive these newer therapies when appropriate.”

Benjamin Kipp, Ph.D.

A dynamic testing approach

Next-generation sequencing is not new to Mayo Clinic Laboratories. The initial MayoComplete solid tumor panel (Mayo ID: MCSTP), which included 514 genes, launched in the spring of 2021. Mayo Clinic Laboratories’ comprehensive NGS hematology panel (Mayo ID: NGSHM), which provides genetic profiling for myeloid neoplasms, has had two previous iterations.

Until now, however, the oncological and hematological NGS test menu was incomplete.

“What makes Mayo Mayo is that we say to our (ordering) clinicians, ‘We will work with you — you tell us which test you need depending on your patient,’” Dr. Kipp says. “We have a large test menu that provides many options for clinicians and patients.

“Many of our laboratory competitors are a one-size-fits all, they have one test and send every test through this way. What Mayo does is say: Sometimes you only need that single gene answer – we have that test for you. If you want to run a disease-specific panel, we can perform that test. If you want to throw a wider net because there are a lot of potential treatments for a specific tumor type, like with a lung cancer patient, we can run the more comprehensive test.”

The new MayoComplete oncology disease-specific panels cover the spectrum of oncology subspecialties, with additional updates planned for 2023. In hematology, implementation of five additional MayoComplete NGS subspecialty panels will take place in 2023.

Comprised of actionable genes carefully selected by a multidisciplinary team of clinicians, geneticists, genetic counselors, and laboratory testing experts, MayoComplete NGS evaluates genes for variations linked to diagnosis, prognosis, and therapeutic response.

“The genetic field is forever evolving and is very dynamic, and we keep a very close eye on the field for new developments,” says Rong He, M.D., co-director of the Molecular Hematopathology Laboratory. “Our advantage first is that we start with a carefully curated gene list.”

Rong He, M.D.

Because the consultants who designed the hematology NGS panels are themselves hematopathologists and use the tests, they are intimately familiar with the disease, Dr. He adds. “We know the ins and outs of the genes, and the genes and regions that we selected — they are clinically informative.”

Genes included on the panels are also recognized as clinically significant and included in consensus group testing guidelines put forth by the World Health Organization, the National Comprehensive Cancer Network, Intercultural Cancer Council, and European LeukemiaNet, among governing bodies.

A deeper dive

In addition to including clinically relevant genes for more types of cancers, the MayoComplete panels also evaluate for microsatellite instability (MSI) status and tumor mutation burden (TMB).

“When immunotherapies were approved for use, there was a need to test for TMB and/or MSI, as these markers help predict whether patients will respond to these drugs,” Dr. Kipp says. “It's known you have to run over 100 different genes to get enough data to actually determine what that tumor mutation burden score is. And so today, if you want to receive a tumor mutation burden score with a microsatellite instability score in addition to rearrangement data, mutation data, indel data, and amplification data, you have to run a large panel.”

The MayoComplete comprehensive panel is not only large enough to provide TMB and MSI scores, it does so using an average amount of tissue, which promotes tissue and cost stewardship, Dr. Kipp adds.

“We're not always running genomes and exomes if it is not wanted by our clinicians — we're just running what clinicians feel is the appropriate number of genes to get the right data,” Dr. Kipp says.  

Targeted NGS panel testing for both solid tumor and hematologic neoplasms is also now highly optimized with the incorporation of a new testing chemistry and improved bioinformatics pipeline, which is the tool used to identify genetic variants.

The current chemistry utilizes unique molecular barcodes to enhance analytical sensitivity with better accuracy in the diagnostic setting. The pipeline components also enable improved indel detection. An important feature of the current NGS oncology panel platform is its easy upgradeability to add pertinent new genes of clinical relevance, Dr. He says. The benefits from these improvements are particularly helpful for assessing individuals with pre-myeloid clonal conditions, who are at risk for progressing to overt malignant myeloid disease, Dr. He adds.

“There's a condition called clonal hematopoiesis of indeterminant potential (CHIP), in which individuals without a hematologic malignancy harbor somatic mutations in bone marrow and blood cells that are associated with myeloid neoplasms, and this is more commonly encountered in people over 60 years old,” Dr. He says. “These individuals are at increased risk of developing a hematologic malignancy, particularly in the setting of unexplained cytopenia.”

Clonal cytopenia of undetermined significance (CCUS) and CHIP typically involve a single gene and are defined by somatic mutations with a variant allele fraction (VAF) of 2%. With a routine detection sensitivity of 2%, the current test will be able to identify additional patient cases in a clinically relevant manner so that they can be followed appropriately, Dr. He explains.

“The NGSHM panel incorporates genes and genetic regions that have been shown to have high clinical utility and validity,” Dr. He says. “There is a challenge to creating a clinically useful test while addressing the increasing genetic complexity in pre-malignant and malignant myeloid disorders, and our current offering meets the needs for a high-value assay in hematologic practice.”

Quality results

To help make sense of the large amounts of data generated by MayoComplete testing, a thorough results review is performed to ensure accuracy.

“Each and every one of these cases is reviewed by a team of genetic experts including technical specialists, genetic counselors, and physician scientists,” Dr. Kipp says. “So each case has multiple sets of eyes on each report assuring that everything is accurate.”

Mayo Clinic genetic counselors do more than interpret findings, Dr. Kipp adds. “Even though this test is looking at just the somatic side, or acquired mutations in the tumor, they can also assess whether some patients may be at risk for a hereditary cancer syndrome based on the genes that are mutated. This is important, as 10% or more of tumors have a hereditary component.”

The interpretive report accompanying test results describes in detail the variant detected and contextualizes the clinical significance from a diagnostic, prognostic, and therapeutic perspective, Dr. He adds.

“Our reports, in comparison to some other labs, are more comprehensive, as we give more detailed information to address the genetic and biologic background and clinical significance of the findings,” Dr. He explains.

In addition to highlighting the clinical utility of the identified variants, reports include information on relevant clinical trials, Dr. Kipp says.

When questions arise, testing specialists can collaborate with Mayo Clinic clinicians to gain their expert opinion on questions.

“If there's something that I am uncertain about, I can pick up the phone and call a colleague who specializes in that tumor type and get their opinion as well,” Dr. Kipp says. “That's a benefit of ordering tests from Mayo Clinic. It's not necessarily just the chemistry, but the expert review team on the tail end of that that allows us to provide the best reports.”

The new MayoComplete oncology panels include sarcoma, melanoma, lung, and colorectal cancers, including gastrointestinal stromal tumors. Within the next year, updates will be made to the neurooncology panel, and new panels will be implemented for renal cell carcinoma, bladder and prostate cancer, gynecological cancer, endometrial cancer, and ovarian, fallopian tube, and peritoneal cancer. In hematology, implementation of MayoComplete NGS panels for B-cell lymphoma, chronic lymphocytic leukemia, T-cell lymphoma, plasma cell myeloma, and histocytic neoplasms will occur in 2023.

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Robin Huiras-Carlson

Robin Huiras-Carlson is a senior marketing specialist at Mayo Clinic Laboratories and a Mayo Clinic employee since 2015. Her writing focuses on specialty testing, innovation, and patient-focused initiatives.