Tumor microvesicles reveal detailed genetic information

February 10, 2011, Massachusetts General Hospital

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 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 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 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 growth," says study co-author Xandra Breakefield, PhD, MGH Neurology and a professor of Neurology at Harvard Medical School.

Related Stories

Recommended for you

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.

Catching up to brain cancer: Researchers develop accurate model of how aggressive cancer cells move and spread

February 15, 2018
A brief chat at a Faculty Senate meeting put two University of Delaware researchers onto an idea that could be of great value to cancer researchers.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.