Mayo Clinic completes first genome-wide analysis of peripheral T-cell lymphomas

Identifies 13 novel alterations in aggressive blood cancer

2012-08-01

(Press-News.org) ROCHESTER, Minn.-- Researchers at Mayo Clinic have completed the world's first genome-wide sequencing analysis of peripheral T-cell lymphomas, unlocking the genetic secrets of this poorly understood and highly aggressive cancer of the immune system.

Andrew Feldman, M.D., a Mayo Clinic pathologist and Damon Runyon Clinical Investigator, and a team of researchers affiliated with Mayo's Center for Individualized Medicine and Mayo Clinic Cancer Center, found 13 genomic abnormalities that were seen in multiple peripheral T-cell lymphomas. Of particular interest, five of these abnormalities relate to production and behavior of the p53 protein -- often called the "guardian of the genome" because of the central role it plays in regulating cell life cycles and, therefore, suppressing cancers.

The study, entitled "Genome-wide Analysis Reveals Recurrent Structural Abnormalities of TP63 and other p53-related Genes in Peripheral T-cell Lymphomas," is scheduled for early release in the online edition of the journal Blood at 9 a.m. on Wednesday, Aug. 1, 2012.

"Every time I diagnose a peripheral T-cell lymphoma, I know that two out of three patients will succumb to that lymphoma," says Dr. Feldman. "That's a very unsatisfying feeling, and I hope that our research can help change those statistics."

Peripheral T-cell lymphomas account for about 12 percent of non-Hodgkin's lymphomas and carry remarkably high mortality rates. Fewer than 35 percent of patients live five years beyond diagnosis.

New diagnostic biomarkers (chemical or genetic clues in the body's system) and treatments aimed at specific subgroups of peripheral T-cell lymphomas could lead to improved outcomes, says Dr. Feldman. Developing these, however, has been a challenge for several reasons. Lymphomas that look remarkably similar under a microscope may differ substantially in their overall prognoses and responses to treatment. Additionally, scientists and doctors have a relatively poor understanding of how peripheral T-cell lymphomas develop and proliferate.

"The most common type of T-cell lymphoma is called 'not otherwise specified.' It's basically a wastebasket diagnosis because we don't understand enough about the specific genetic abnormalities to be able to pinpoint subtypes of T-cell lymphomas that might trigger different treatments by the treating oncologist," says Dr. Feldman.

Dr. Feldman's study will be used to improve diagnostic tests and develop targeted treatments for peripheral T-cell lymphoma.

Among the key findings in the genomic abnormalities of peripheral T-cell lymphoma are: Thirteen recurrent chromosomal rearrangements Five of the 13 rearrangements involve p53-related genes, important for tumor-suppressor function Novel rearrangements involving the TP53 homologue and TP63, which were associated with shortened survival times Four interchromosomal abnormalities, including the previously known ALK and DUSP22-IRF4 translocations ### This study was supported by the Mayo Clinic Center for Individualized Medicine, a generous gift from Edith and Bernie Waterman, the Damon Runyon Foundation, an Experimental Pathology Development Award from the Mayo Clinic Department of Laboratory Medicine and Pathology, and gifts from other benefactors.

Authors of the study are George Vasmatzis, Ph.D., Sarah Johnson, Ryan Knudson, Rhett Ketterling, M.D., Esteban Braggio, Ph.D., Rafael Fonseca, M.D., David Viswanatha, M.D., Mark Law, N. Sertac Kip, M.D., Ph.D., Stefan Grebe, M.D., Lori Frederick, Bruce Eckloff, E. Aubrey Thompson, Ph.D., Dragana Milosevic, Julie Porcher, Yan Asmann, Ph.D., David Smith, Ph.D., Irina V Kovtun, Ph.D., Stephen Ansell, M.D., Ph.D., Ahmet Dogan, M.D., Ph.D., and Andrew Feldman, M.D., all of Mayo Clinic; Marshall Kadin, M.D., of Roger Williams Medical Center in Providence, R.I.; and Nazan Özsan, M.D., of Ege University in Izmir, Turkey. About the Mayo Clinic Center for Individualized Medicine The Center for Individualized Medicine discovers and integrates the latest in genomic, molecular and clinical sciences into personalized care for each Mayo Clinic patient. For more information, visit http://mayoresearch.mayo.edu/center-for-individualized-medicine.

As a leading institution funded by the National Cancer Institute, 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 507-538-7623.

About Mayo Clinic Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit MayoClinic.com or MayoClinic.org/news.

ELSE PRESS RELEASES FROM THIS DATE:

Scientists discover molecular link between circadian clock disturbances and inflammatory diseases

2012-08-01

LA JOLLA, CA ---- Scientists have known for some time that throwing off the body's circadian rhythm can negatively affect body chemistry. In fact, workers whose sleep-wake cycles are disrupted by night shifts are more susceptible to chronic inflammatory diseases such as diabetes, obesity and cancer. Researchers at the Salk Institute for Biological Studies have now found a possible molecular link between circadian rhythm disturbances and an increased inflammatory response. In a study published July 9 in Proceedings of the National Academy of Sciences, the Salk team found ...

Fruit flies on methamphetamine die largely as a result of anorexia

2012-08-01

CHAMPAIGN, Ill. — A new study finds that fruit flies exposed to methamphetamine drastically reduce their food intake and increase their physical activity, just as humans do. The study, which tracked metabolic and behavioral changes in fruit flies on meth, indicates that starvation is a primary driver of methamphetamine-related death in the insects. The new findings are described in The Journal of Toxicological Sciences. The abuse of methamphetamine can have significant harmful side effects in humans. It burdens the body with toxic metabolic byproducts and weakens the ...

AAO-sponsored research shows cataract surgery can reduce hip fracture risk

2012-08-01

SAN FRANCISCO – August 1, 2012 – A major study of Medicare beneficiaries shows that the risk of hip fractures was significantly reduced in patients who had had cataract surgery, compared to patients who did not undergo the procedure. Published in the August edition of the Journal of the American Medical Association (JAMA) the researchers believe their study is the first to demonstrate that cataract surgery reduces the rate of fractures in older patients with vision loss. This suggests that cataract surgery could be an effective intervention to help prevent fractures and ...

New study suggests clinicians overlook alcohol problems if patients are not intoxicated

2012-08-01

Medical staff struggle to spot problem drinking in their patients unless they are already intoxicated, according to research by the University of Leicester. The work led by Dr Alex J Mitchell, consultant at Leicestershire Partnership NHS Trust and honorary senior lecturer at the University, reveals that clinical staff often overlook alcohol problems in their patients when they do not present intoxicated. In a new study published in the British Journal of Psychiatry today (1 August) involving 20,000 patients assessed for alcohol problems by medical staff, all clinicians ...

DMP module on heart failure: Current guidelines indicate some need for revision

2012-08-01

The German Institute for Quality and Efficiency in Health Care (IQWiG) published the results of a literature search for evidence-based clinical practice guidelines on the treatment of people with heart failure. The aim of the report is to identify those recommendations from current guidelines of high methodological quality that may be relevant for the planned revision of the module "heart failure" in the disease management programme (DMP) for coronary heart disease (CHD). According to the results of the report, there is no compelling need for revision of any part of the ...

Better student preparation needed for university maths

2012-08-01

Moving from sixth form, or college, into higher education (HE) can be a challenge for many students, especially those who start mathematically demanding courses. Life prior to university focuses on achieving maximum examination success to be sure of a place. Faced with this pressure, school and college maths courses pay little attention to preparing students to use maths in other areas of study according to a project funded by the Economic and Social Research Council (ESRC). A student's ability to apply mathematical reasoning is critical to their success, especially in ...

Strangers on a bus: Study reveals lengths commuters go to avoid each other

2012-08-01

You're on the bus, and one of the only free seats is next to you. How, and why, do you stop another passenger sitting there? New research reveals the tactics commuters use to avoid each other, a practice the paper, published in Symbolic Interaction describes as 'nonsocial transient behavior.' The study was carried out by Esther Kim, from Yale University, who chalked up thousands of miles of bus travel to examine the unspoken rules and behaviors of commuters. Over three years Kim took coach trips across the United States. Kim's first trip, between Connecticut and New ...

Global 'sleeplessness epidemic' affects an estimated 150 million in developing world

2012-08-01

Levels of sleep problems in the developing world are approaching those seen in developed nations, linked to an increase in problems like depression and anxiety. According to the first ever pan-African and Asian analysis of sleep problems, led by Warwick Medical School at the University of Warwick, an estimated 150 million adults are suffering from sleep-related problems across the developing world. The results are published in a study in the journal Sleep. Warwick Medical School researchers have found a rate of 16.6 per cent of the population reporting insomnia and ...

Too cool to follow the law

2012-08-01

So-called glass-formers are a class of highly viscous liquid materials that have the consistency of honey and turn into brittle glass once cooled to sufficiently low temperatures. Zhen Chen and his colleagues from Arizona State University, USA, have elucidated the behaviour of these materials as they are on the verge of turning into glass in an article about to be published in EPJ E¹. Although scientists do not yet thoroughly understand their behaviour when approaching the glassy state, this new study, which relies on an additional type of dynamic measurements, clearly ...

Rewarding work for butterflies

2012-08-01

Butterflies learn faster when a flower is rewarding than when it is not, and females have the edge over males when it comes to speed of learning with rewards. These are the findings of a new study, by Dr. Ikuo Kandori and Takafumi Yamaki from Kinki University in Japan. Their work, published online in Springer's journal Naturwissenschaften - The Science of Nature, is the first to investigate and compare the speed at which insects learn from both rewarding and non-rewarding experiences. Learning is a fundamental mechanism for adjusting behavior to environmental change. ...

LAST 30 PRESS RELEASES:

Mathematical model illuminates how environment impacts life choices of salmon

Houston Methodist researchers shed light on increased rates of severe human infections caused by Streptococcus subspecies

Change of ownership in home health agencies may lead to increased Medicare spending and reduced staffing levels, according to UTHealth Houston research