ROCHESTER, Minn. — An important new clue for preventing and treating brain tumors known as gliomas has been identified in research led by the Lunenfeld-Tannenbaum Research Institute (LTRI) at Mount Sinai Hospital in Toronto and Mayo Clinic Comprehensive Cancer Center and Mayo Clinic Center for Individualized Medicine. The study, published in the journal Science, provides a rare window into the biological changes behind glioma development.

Researchers found that animal models who carry a change in DNA known as germline alteration rs55705857 developed gliomas much more frequently — and in half the time — compared to animal models without the alteration. In addition to brain tumors, the findings are relevant to other cancers and diseases.

"While we understand much of the biologic function of germline alterations within genes that code for proteins, we know very little about the biologic function of germline alterations outside of genes that code for proteins. In some way, these germline alterations interact with other mutations in cells to accelerate tumor formation," says co-lead author Robert Jenkins, M.D., Ph.D., a genetics researcher at Mayo Clinic in Rochester. "Based on this new understanding of its mechanism of action, future research may lead to novel and specific therapies that target the rs55705857 alteration."

The study offers new knowledge that may help clinicians determine, pre-surgery, whether a patient has a glioma.

"We expected that rs55705857 would accelerate low-grade glioma development, but we were surprised by the magnitude of that acceleration," says co-lead author Daniel Schramek, Ph.D., a researcher at Lunenfeld-Tannenbaum Research Institute.

There are many alterations, likely thousands, outside of genes associated with the development of cancer and other diseases, but the mechanism of action is only understood for very few, Dr. Schramek says.

This study demonstrates that, with the tools of modern molecular/cell biology, it is possible to decipher much of the mechanism of action of such alterations.

Dr. Jenkins is a Ting Tsung and Wei Fong Chao Professor in Individualized Medicine Research and researcher in Mayo Clinic’s Department of Laboratory Medicine and Pathology.

Dr. Schramek is a senior investigator and holds a Kierans & Janigan Research Chair at the LTRI and is an associate professor, Department of Molecular Genetics, Faculty of Medicine, University of Toronto.

###

About Mayo Clinic Comprehensive Cancer Center
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining new boundaries in possibility, focusing on patient-centered care, developing novel treatments, training future generations of cancer experts, and bringing cancer research to communities. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs that are changing approaches to cancer prevention, screening and treatment, and improving the lives of cancer survivors. Visit the Mayo Clinic Comprehensive Cancer Center Blog for news, information and stories from Mayo Clinic’s cancer experts and patients.

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

About the Lunenfeld-Tanenbaum Research Institute
The Lunenfeld-Tanenbaum Research Institute (LTRI), part of Sinai Health, is a leading biomedical research centre, ranking amongst the top biomedical research institutes in the world. Established in 1985, the institute is profoundly advancing understanding of human biology in health and disease. Many of the breakthroughs that began as fundamental research have resulted in new and better ways to prevent, diagnose and treat prevalent conditions. The institute is affiliated with the University of Toronto and is focused on women’s and infants’ health, cancer biology, stem cell biology and regenerative medicine, neurobiology, diabetes, arthritis, health systems research, population health services and solutions, and systems biology. www.lunenfeld.ca.

Media contacts:

• Kelley Luckstein, Mayo Clinic Communications Department, newsbureau@mayo.edu
• Jennifer Specht, Sinai Health Communications Department, jennifer.specht@sinaihealth.ca

The post Research provides critical information about the size and growth speed of gliomas appeared first on Mayo Clinic News Network.

Alex Kraatz is a creative, determined optimist who loves playing the guitar, taking photos, and spending time with his family. Softspoken with a gentle nature, Alex’s mettle isn’t immediately obvious. But there is no doubt, Alex is a fighter to the core.

Just 34 years old, Alex has survived not one, but two different types of brain tumors. Both tumors, which occurred 20 years apart, had the capacity to kill Alex. Surrender, however, isn’t in Alex’s wheelhouse.

Nor is it in his mother’s. Linda knew there was a better treatment path for Alex when his local care providers couldn’t offer therapy needed to treat Alex’s tumors. Fueled by an unrelenting desire to save her child, Linda did not hesitate to travel to Mayo Clinic, which held the promise of a lifesaving remedy.

At 9 years old and again at age 29, Alex underwent brain surgery, radiation, and chemotherapy at Mayo Clinic in Rochester, Minnesota, to treat the tumors. As part of treatment for Alex’s second tumor, genetic testing performed at Mayo Clinic Laboratories revealed characteristics that helped Alex’s care team develop a targeted treatment plan.

“He is such a unique case,” says neuro-oncologist Michael Ruff, M.D., who treated Alex. “It’s so unusual to have this sort of situation where you have the second tumor in the same location that is managed quite differently. An adult medulloblastoma, there’s less than one in a million chance of that, and a glioblastoma potentially coming from the childhood tumor has to be far less than that.”

Neuro oncological testing, both a chromosomal microarray and an expanded gene panel, performed in 2017 on Alex’s second tumor revealed the lesion was a grade 4 glioblastoma. But that is not all testing showed.

“They did a test called MGMT, which looks at methyltransferase, and he was positive for that,” says Robert Jenkins, M.D., Ph.D., a Mayo Clinic pathologist and cancer geneticist who helped consult on Alex’s testing. “This is a test done on all glioblastoma and if they are positive, they have a chance of responding to a specific kind of chemotherapy.”

That testing helped Alex’s care team choose a treatment plan that gave him the best chance to survive.

While the medical savvy of Alex’s care team and cutting-edge testing and treatment maximized his success, Alex’s attitude was the force that has pulled him through his daunting medical journey, Linda says.

“He was always up to the challenge,” she says. “He was the inspiration for the rest of us.”

Surviving and thriving

Alex’s journey hasn’t been easy. The surgery required to treat his first tumor, a medulloblastoma, resulted in brain tissue damage that altered Alex’s appearance and abilities.

“We did learn at that time that he was going to have partial facial paralysis because the muscles were disturbed,” Linda says. “One eye didn’t close for a long, long time. He lost his balance, some of his fine motor skills, and some IQ and memory. But he was alive, and that’s what really mattered to us.”

Following surgery, Alex received six weeks of radiation to his brain and spinal column followed by two weeks of targeted radiation to the tumor’s location in his brain. The radiation treatments, which required Alex to wear a protective mask, were intense, Alex says. “I remember being really worried during the radiation procedure, and when I closed my eyes all I could see was lightning.”

During that time period, Alex also relearned how to walk and take care of himself.

“It was a matter of him having to get used to his body again,” explains Linda, adding that one of the hardest parts of Alex’s journey was coming to terms with his new appearance.

“He was received differently because his face was different,” Linda says. “Even some of his teachers didn’t get it. At the time, in some ways it was like grieving the loss of one child and trying to accept a new child.”

Alex believes optimism has been an important part of managing his challenges. “I didn’t always have a good outlook, but it’s helped me to deal with more over the years,” he says.

Two years after his initial tumor diagnosis, Alex’s family moved from their hometown in South Dakota to Minneapolis, where Alex started attending a much larger school. With more opportunities in arts and music, Alex flourished. He joined the track team and ran long distance events. Alex and some friends started a band. By graduation, Alex was attending mainstream classes and had been awarded a scholarship for photography at Minneapolis Community and Technical College.

Alex Kraatz is a creative, determined optimist who loves playing the guitar, taking photos, and spending time with his family.

Through it all, Alex received regular follow-up imaging, none of which showed the tumor was threatening to return. At the 20-year anniversary of this diagnosis and treatment, the family celebrated.

“They told me 20 years is the mark where you consider yourself to be cancer free, and we had a party,” Linda says.

Just weeks after that milestone, Alex’s head began to hurt. His neck started to ache. Vomiting followed. “He started throwing up this clear fluid and the minute I saw it, I knew,” Linda says.

Devastation, then hope

A visit to an area oncologist confirmed Linda’s fears. Alex’s tumor had returned.

“The scan he showed us had what looked like a hurricane in the back of Alex’s head; it was just huge,” Linda says. “They did a biopsy and found it was glioblastoma. The surgeon said he thought he could get 60% to 70% of the tumor because it was so close to his brain stem, and with the surgery and chemotherapy he could live another eight months. They were preparing us for the end and didn’t give us a lot of hope.”

So Linda called Mayo Clinic.

“THE DOCTOR AT THE OTHER END OF THE LINE SAID, ‘WE’LL LOOK AT THIS AND GET BACK TO YOU,’” LINDA SAYS. “WITHIN HOURS THE PHONE RANG, AND IT WAS DR. (PAUL) BROWN, WHO TOLD US TO HOLD THE PRESSES AND STOP WHAT WE WERE DOING. HE SAID MAYO HAS PROTON BEAM RADIATION AND SURGEONS WHO THINK THEY CAN DO BETTER.”

Linda says the family cancelled everything and immediately went to Mayo Clinic. “We walked back into Mayo Clinic and it was like being home,” she says. “And here we are, five years later.”

Within days, Alex underwent his second brain surgery. Performed by neurosurgeon Terry Burns, M.D., Ph.D., the surgery resulted in a 97% resection of the tumor. Following the operation, laboratory testing revealed surprising characteristics about the tumor.

A chromosomal microarray (Mayo ID: CMAPT) and an expanded gene panel (Mayo ID: NONCP) looked for copy number variations, and genetic mutations and rearrangements. Based on those evaluations, Alex’s team confirmed his second tumor was a grade 4 glioblastoma — not a recurrent medulloblastoma, which requires a completely different treatment regimen.

While it is impossible to say with certainty that the treatment Alex received for the first tumor is related to the second, there has been a growing recognition among neuro oncologists that glioblastoma can develop secondary to prior therapy.

“Once cells have been treated with radiation and chemotherapy, those cells are pretty damaged,” Dr. Jenkins says. “They may not survive very well in the milieu of the brain or may just sit there not dying and then something else happens, which gives the cells more of a survival advantage and a secondary tumor can grow back.”

Because different types of glioblastoma respond differently to therapy, an MGMT promoter methylation (Mayo ID: MGMT) was performed to gauge the tumor’s susceptibility to treatment.

“There are patients like Alex who have remarkable responses when their secondary glioma, or glioblastoma, is treated with chemotherapy and radiation, and it seems he is in that group,” Dr. Jenkins says.

Based on those test results, Alex’s care team started him on proton beam radiation. He was also prescribed chemotherapy pills. Finally, Alex received Optune therapy, which is a wearable, portable treatment that creates electric fields, known as tumor treating fields, that disrupt cancer cell division.

To date, follow-up imaging of Alex’s brain — which he typically receives every four months at Mayo Square in Minneapolis — have not shown any new cancer growth.

According to Dr. Ruff, glioblastoma survival beyond five years is achieved by about 13% of patients. For Alex to have survived a childhood brain tumor and then beat a second is remarkable.

“THIS IS A VERY RARE OCCURRENCE,” DR. RUFF SAYS. “THAT ALEX HAS RETURNED TO THE LEVEL OF FUNCTION THAT HE HAS WHERE HE’S STILL PLAYING DRUMS AND FULLY INDEPENDENT IN HIS DAY-TO-DAY LIFE, I’M JUST INCREDIBLY IMPRESSED WITH THIS YOUNG MAN. HE HAS SUCH A STRONG SPIRIT.”

This story first appeared on the Mayo Clinic Laboratories blog.

The post Against the odds appeared first on Mayo Clinic News Network.

This novel chromosome test finds the “breaks” in gene rearrangements that other tests can’t.

ROCHESTER, Minn. — Mayo Clinic has launched a first-of-its-kind clinical test that will be used to help patients who may be at a diagnostic “dead end” with other genetic testing. The mate-pair sequencing test can identify chromosome alterations or “breakpoints” involved in chromosome rearrangements, pinpointing the precise genes involved.

“Until now, this type of test was not available for clinical use,” says Robert Jenkins, M.D., Ph.D., a Mayo Clinic pathologist and cancer geneticist. “The assay can be really useful in knowing which genes are at those breakpoints because current chromosome studies cannot provide that level of resolution.”

The new test examines all 23 pairs of chromosomes in a single test and could help clinicians and patients avoid unnecessary and potentially expensive extra tests when searching for a chromosome abnormality. In addition, because the test looks at all chromosomes, it may be able to identify previously unknown alterations that may provide patients with a diagnosis or possibly change their treatment. The test is available to Mayo Clinic patients and health care providers worldwide through Mayo Medical Laboratories, the global reference laboratory of Mayo Clinic.

Nicole Lynn Hoppman, Ph.D., a Mayo Clinic molecular cytogeneticist who focuses on testing and research of congenital disorders, says, “It can be emotionally difficult for families to go on a medical journey and never really arrive at an explanation. This test offers earlier answers for young patients with neurological or developmental delays who have been part of a diagnostic odyssey.”

Cancer researchers say this test is especially useful for understanding the underlying biology of a patient’s tumor. Knowing the nature of the gene rearrangement could change the way an individual’s cancer is managed. “Being able to put disease types into diagnostic categories is important to patients,” says Dr. Jenkins.

George Vasmatzis, Ph.D., a Mayo Clinic genomicist, is the primary developer of the software and experimental procedures that led to the new test. Dr. Vasmatzis co-directs the Biomarker Discovery Program within the Mayo Clinic Center for Individualized Medicine along with John Cheville, M.D., a Mayo Clinic pathologist. “Our mate-pair sequencing technology is transformative, allowing genomic information critical to patient care to be determined comprehensively, accurately and quickly,” says Dr. Vasmatzis. “Our program is working closely with the Mayo Clinic Medical Genome Facility and the Department of Laboratory Medicine and Pathology to explore additional mate-pair next-generation sequencing applications.”

This work was supported by the Mayo Clinic Center for Individualized Medicine and the Mayo Clinic Department of Laboratory Medicine and Pathology.

About the mate-pair sequencing test (Test IDs: MTRBL, MTRTI, and MTRBM)
For congenital chromosome abnormalities, the mate-pair sequencing test is appropriate for individuals with an apparently balanced congenital chromosome rearrangement of uncertain clinical significance.

For oncologic and hematologic specimens, the mate-pair sequencing test is appropriate for individuals with previously detected acquired chromosomal abnormalities.

This next-generation sequencing technology can aid in the further characterization of chromosome abnormalities by sequencing the entire genome and creating a structural map of the genome. The technique enables the detection of chromosome rearrangements, which allows for determination of genes at or near the breakpoints.

###

About Mayo Medical Laboratories/Department of Laboratory Medicine and Pathology
The Mayo Clinic Department of Laboratory Medicine and Pathology and its reference laboratory Mayo Medical Laboratories provide advanced laboratory testing and pathology services to support 4,000 health care organizations around the world. Revenue from this testing is used to support medical education and research at Mayo Clinic, a nonprofit worldwide leader in medical care, research, and education for people from all walks of life. Complemented by collaborations with diagnostic and biotechnology companies, the department maintains a robust diagnostic test-development program, launching more than 150 new tests each year.

About the Mayo Clinic Center for Individualized Medicine
The Mayo Clinic Center for Individualized Medicine discovers, translates and applies new findings in genomic research into individualized medicine products and services for patients everywhere. For more information, visit mayoresearch.mayo.edu/center-for-individualized-medicine.

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to clinical practice, education, and research, providing expert, comprehensive care to everyone who needs healing. For more information, visit mayoclinic.org/about-mayo-clinic or newsnetwork.mayoclinic.org/.

MEDIA CONTACT
Gina Chiri-Osmond, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu

The post Mayo Clinic launches first-in-world mate-pair sequencing test that locates “breakpoints” of chromosome rearrangements appeared first on Mayo Clinic News Network.

Mayo Clinic researchers found that the number of HER2-positive breast cancers doubled after testing guidelines were changed by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) in 2013. “The new guidelines were established to reduce the number of equivocal cases, where HER2 status is uncertain, but we found that they did just the opposite,” says senior study author Robert Jenkins, M.D., Ph.D., the Ting Tsung and Wei Fong Chao Professor of Individualized Medicine Research and Professor of Laboratory Medicine and Pathology at Mayo Clinic. “The number of equivocal cases went up, resulting in additional testing and a much larger number of women with cancers ultimately labeled as HER2-positive.

According to Breastcancer.org, more than 10 percent of women will develop breast cancer in their lifetime. In the U.S. alone, the American Cancer Society estimates there will be more than 246,000 new cases of invasive breast cancer diagnosed this year, along with 61,000 new cases of noninvasive breast cancer. All newly diagnosed breast cancers are tested for human epidermal growth factor receptor 2 (HER2), a molecule that promotes the growth of cancer cells. HER2-positive cancers tend to be more aggressive and spread more quickly than other breast cancers.

Dr. Jenkins says the development of drugs like trastuzumab (Herceptin) and lapatinib (Tykerb) that target HER2 have greatly improved the prognosis of patients with HER2-positive breast cancer, but it is not clear what level of HER2 is needed on cancer cells for these targeted therapies to be effective. Therefore, he says, it is critical that clinicians accurately determine the HER2 status of a particular cancer. HER2 testing is performed using two methods: immunohistochemistry, which detects how much of the HER2 protein is present on cancer cells, and fluorescence in-situ hybridization (FISH), which measures how many copies of the HER2 gene are inside each cell.

The U.S. Food and Drug Administration (FDA) approved the first HER2 testing guidelines for determining eligibility for HER2-directed therapy for breast cancer in 1998. The American Society of Clinical Oncology/College of American Pathologists published a new set of guidelines in 2007 (AC2007), which were updated in 2013 (AC2013). The latest guidelines changed the cut-off for equivocal and positive cases.

Dr. Jenkins and his colleagues hypothesized that the new criteria outlined in AC2013 would lead to an increase in the number of breast cancers that test HER2-positive. They analyzed FISH results for 2,851 breast cancer cases referred to the Mayo Clinic Cytogenetics Laboratory for FISH testing between November 2013 and October 2014, and then compared the prevalence of HER2 FISH amplification using the three guidelines.

MEDIA CONTACT: Joe Dangor, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu

In their analysis, the researchers found a near doubling in the proportion of HER2 FISH-positive cases interpreted using AC2013 (23.6 percent), compared to the FDA criteria (13.1 percent) or AC2007 (11 percent). The Mayo researchers previously reported a 13 percent HER2-positivity rate using the FDA criteria in their clinical practice in 2000, and that rate had remained constant until the implementation of AC2013. Since the implementation of AC2013, an additional 10-15 percent of women with breast cancer are considered eligible for HER2-directed therapies, even though it is unknown if they would benefit from addition of HER2-directed treatments.

“Women who receive false positive results are not only exposed to the risks of HER2-directed therapies, but they also miss out on the treatments that could be effective against their cancer. That is counter to the goal of personalized medicine, which is to give the right drug to the right patient at the right time,” says Dr. Jenkins. “Given the medical, financial and psychosocial aspects of these targeted therapies, it is prudent that we prospectively identify the most optimal candidates for treatment.”

Dr. Jenkins says that the recent National Surgical Adjuvant Breast and Bowel Project B-47 trial could provide insight into whether the additional patients labeled as HER2-positive by AC2013 actually will benefit from HER2-directed therapies. Ultimately, he says, the decision to use such targeted therapies should be taken only after carefully considering the risks and benefits by patients and their physicians, as well as any additional information that can be gleaned from other HER2 tests results, including immunohistochemistry.

Co-authors are:

• Mithun Vinod Shah, M.D. Ph.D., Mayo Clinic
• Anne Wiktor, Mayo Clinic
• Reid Meyer, Mayo Clinic
• Kathleen Tenner, Mayo Clinic
• Karla Ballman, Ph.D.
• Stefan Green, Mayo Clinic
• William Sukov, M.D., Mayo Clinic
• Rhett Ketterling, M.D., Mayo Clinic
• Edith Perez, M.D., Mayo Clinic

The study was supported by grants from the National Cancer Institute of the National Institutes of Health.

About the Mayo Clinic Cancer Center
As a leading institution funded by the National Cancer Institute, the Mayo Clinic Cancer Center conducts basic, clinical and population science research, translating discoveries into improved methods for prevention, diagnosis, prognosis and therapy. For information on cancer clinical trials, call the clinical trials referral office at 1-855-776-0015 (toll-free).

### 

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit http://www.mayoclinic.org/about-mayo-clinic or https://newsnetwork.mayoclinic.org/.

The post Updated Testing Guidelines Make More Women Eligible for Herceptin, yet Benefit Uncertain appeared first on Mayo Clinic News Network.

Click here to listen to the Mayo Clinic Radio podcast.

The post Brain Cancer/Human Microbiome/Stool Transplantation: Mayo Clinic Radio appeared first on Mayo Clinic News Network.

Myth or Matter-of-Fact: About one-third of all brain cancers are gliomas.

Mayo Clinic Radio is available on iHeartRadio.

Listen to the program at 9:05 a.m. CT, Saturday, January 2 and follow #MayoClinicRadio.

Access archived shows.

Mayo Clinic Radio is a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

The post Mayo Clinic Radio: Brain Cancer/Human Microbiome/Stool Transplantation appeared first on Mayo Clinic News Network.

Myth or Matter-of-Fact: About one-third of all brain cancers are gliomas.

Listen to the program at 9:05 a.m. CT, Saturday, January 2.

Follow #MayoClinicRadio and tweet your questions.

Mayo Clinic Radio is available on iHeartRadio.

Mayo Clinic Radio is a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

Access archived shows.

The post Mayo Clinic Radio: Brain Cancer/Human Microbiome/Stool Transplantation appeared first on Mayo Clinic News Network.

Myth or Matter-of-Fact: Men are more likely than women to develop Parkinson's disease.

Mayo Clinic Radio is available on iHeartRadio.

Listen to this program at 9:05 a.m. CT Saturday, October 31 and follow #MayoClinicRadio.

Access archived shows.

Mayo Clinic Radio is a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

The post Mayo Clinic Radio appeared first on Mayo Clinic News Network.

Myth or Matter-of-Fact: Men are more likely than women to develop Parkinson's disease.

Miss the show?  Here's the Mayo Clinic Radio podcast.

Follow #MayoClinicRadio and tweet your questions.

Mayo Clinic Radio is available on iHeartRadio.

Mayo Clinic Radio is a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

Access archived shows.

The post Mayo Clinic Radio: Parkinson’s Disease/Retinal Detachment/Halloween Safety appeared first on Mayo Clinic News Network.

According to the National Cancer Institute, more than 23,000 new cases of brain cancer were diagnosed in the U.S. last year. Of those, about one-third were gliomas ... a type of brain cancer that's particularly hard to treat. On this week's program, Dr. Robert Jenkins, a pathologist and specialist in laboratory genetics, explains new research that may lead to more effective treatments for gliomas. And scientist Dr. Richard Vile describes how a teenage girl with brain cancer changed the focus of his research. Also on the program, orthopedic surgeon Dr. John Sperling talks about rotator cuff injury ... what it is and how it's repaired. And, the Consumer Product Safety Commission reports that about 240 people go to the emergency room each day during the weeks around the Fourth of July with fireworks-related injuries. Surgeon and trauma specialist Dr. Donald Jenkins discusses the hazards of using fireworks at home.

Myth or Matter-of-Fact: Research shows that of the different types of gliomas, all are genetically the same.

Mayo Clinic Radio is available on iHeart Radio.

Click here to listen to the program on Saturday, June 27, at 9:05 a.m., and follow #MayoClinicRadio.

To find and listen to archived shows, click here.

Mayo Clinic Radio is a weekly one-hour radio program highlighting health and medical information from Mayo Clinic. The show is taped for rebroadcast by some affiliates.

The post MAYO CLINIC RADIO appeared first on Mayo Clinic News Network.