The Massachusetts General Hospital (MGH) research team that first discovered tumor-associated RNA in tiny membrane-enclosed sacs released into the bloodstream by cancer cells has now found that these microvesicles also contain segments of tumor DNA, including retrotransposons – also called "jumping genes" – that copy and insert themselves into other areas of the genome. The investigators' report, which has been published in Nature Communications, is the first to show that microvesicles are involved in transferring retrotransposons between cells.
"Retrotransposons' action of self-copying and reinserting themselves into the genome leads to genetic instability," says Johan Skog, PhD, who led the current study while an investigator in the MGH Neurology Service. "Many researchers have proposed this as a mechanism for genetic diversity and for evolution. Retrotransposons are known to be upregulated in cancer, and discovering them in microvesicles that can be found in all body fluids suggests they could be useful biomarkers to help understand tumor progression and monitor treatment response."
Skog was lead author of a 2008 study that first identified tumor-associated RNA in microvesicles, also called exosomes, released by the deadly adult brain tumor glioblastoma. To further investigate the ability of microvesicles to reflect the genetic status of tumors, in the current study the MGH team analyzed the nucleic acid contents of microvesicles from glioblastomas, from two types of pediatric brain tumors, and from malignant melanomas.
They found that the microvesicles contained tumor DNA as well as RNA and that microvesicles from one of the pediatric tumors studied had elevated levels of both DNA and RNA from the oncogene c-Myc, which correlated with the gene's expression in that tumor. "We showed that amplification of c-Myc was present in microvesicles whenever it was present in the donor cell and that microvesicle analysis can reveal oncogene expression in the original tumor," explains Leonora Balaj of MGH Neurology, the first author of the study.
High levels of retrotransposon-associated RNA sequences were also detected in tumor microvesicles, and the investigators found those microvesicles could transfer their contents into normal cells. "One of the most important functions of tumor-derived microvesicles may be modification of normal cells in the microenvironment to make them more supportive of tumor growth," says study co-author Xandra Breakefield, PhD, MGH Neurology and a professor of Neurology at Harvard Medical School.
Skog is now the director of research for Exosome Diagnostics, the company that licensed the work described in the 2008 paper, and continues to consult with Breakefield's research team. Additional co-authors of the Nature Communications report are Ryan Lessard, MGH Neurology; Lixin Dai, Johns Hopkins School of Medicine; and Yoon-Jae Cho, MD, and Scott Pomeroy, MD, PhD, Children's Hospital Boston. The study was supported by grants from the National Cancer Institute, the Wenner-Gren Foundation, and Stiftelsen Olle Engkvist Byggmastare.
Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
Sue McGreevey | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy