Findings from the genetic sequencing of Burkitt lymphoma, an aggressive form of lymphoma, could be used to develop new drugs or aim existing therapies at mutations known to be susceptible. The researchers published their findings online Sunday, Nov. 11, 2012, in the journal Nature Genetics.
"This study lays out the most common genetic alterations in the disease, and allows us to understand the biology of the disease so we can design better therapies," said Sandeep S. Dave, M.D., MBA, MS, associate professor at Duke and senior author of the study.
Dave and colleagues sequenced the first complete Burkitt lymphoma genome, plus the genes from 59 additional Burkitt cases and 94 diffuse large B cell lymphomas, which share many of the same characteristics of Burkitt lymphoma. Similarities between the malignancies can often lead to mistaken diagnoses and failed treatments.
The researchers reported striking differences in the gene mutation patterns of Burkitt lymphomas vs. the diffuse large B cell lymphomas.
"It's important that doctors make the right diagnosis for Burkitt lymphoma, which can be cured with the correct therapies," Dave said. "But if misdiagnosed and given the standard chemotherapy regimes for diffuse large B cell lymphomas, Burkitt lymphoma patients invariably relapse."
The analysis identified 70 genes that were frequently mutated in the Burkitt lymphomas, including a number of genes that were identified in cancer for the first time. One of the newly identified gene mutations, ID3, appeared in 34 percent of the Burkitt cases, but was not evident in any of the diffuse large B cell lymphomas. The mutation has a silencing effect on a gene that suppresses cell growth, enabling cells to multiply.
Dave said this alteration alone may not cause cancer, but when it occurs along with the MYC gene mutations that are common in Burkitt lymphoma and other malignancies, it works like an accelerant to fuel tumor growth. That finding could prove helpful for developing a new drug to function like a normal ID3 gene and suppress cancer cell proliferation in lymphomas as well as numerous other cancers.
"If we can find a way to mimic ID3, restoring the function of the gene to slow the growth of tumors, this could provide a new treatment approach," Dave said. "We have experiments that suggest this is the case, but much more research is needed. This work provides a starting point."
Study co-authors from Dave's laboratory at Duke include first author Cassandra Love, plus Zhen Sun, Dereje Jima, Guojie Li, Jenny Zhang, Adrienne Greenough, Andrea B. Moffitt, Matthew McKinney, Vladimir Grubor; from the Duke Department of Statistics, co-authors include Anjishnu Banerjee and David B. Dunson; and from the Hematologic Malignancies Research Consortium, an international consortium of more than a dozen institutions around the world, co-authors are Rodney Miles, Kristy L. Richards, Cherie H. Dunphy, William W.L. Choi, Gopesh Srivastava, Shawn Levy, Patricia L. Lugar, David Rizzieri, Anand S. Lagoo, Leon Bernal-Mizrachi, Karen P. Mann, Christopher R. Flowers, Kikkeri N. Naresh, Andrew M. Evens, Amy Chadburn, Leo I. Gordon, Magdalena B. Czader, Javed I. Gill and Eric D. Hsi.
The study was funded with a donation from Charles and Daneen Stiefel, and grants from the American Cancer Society and the National Institutes of Health (R21CA156168 and R01CA136895).
Sarah Avery | EurekAlert!
Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory
‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
08.12.2017 | Event News
07.12.2017 | Event News
05.12.2017 | Event News
11.12.2017 | Physics and Astronomy
11.12.2017 | Materials Sciences
11.12.2017 | Earth Sciences