Featured Research

from universities, journals, and other organizations

Slow growth of childhood brain tumors linked to genetic process seen in skin moles

Date:
June 24, 2011
Source:
Johns Hopkins Medical Institutions
Summary:
Researchers have found a likely explanation for the slow growth of the most common childhood brain tumor, pilocytic astrocytoma. Using tests on a new cell-based model of the tumor, they concluded that the initial process of tumor formation switches on a growth-braking tumor-suppressor gene, in a process similar to that seen in skin moles.

Johns Hopkins researchers have found a likely explanation for the slow growth of the most common childhood brain tumor, pilocytic astrocytoma. Using tests on a new cell-based model of the tumor, they concluded that the initial process of tumor formation switches on a growth-braking tumor-suppressor gene, in a process similar to that seen in skin moles.

Related Articles


The findings, published in the June 1 issue of Clinical Cancer Research, could lead to better ways of evaluating and treating pilocytic astrocytomas.

"These tumors are slow-growing to start with, and sometimes stop growing, and now we have a pretty good idea of why that happens," says Charles G. Eberhart, M.D., Ph.D., associate professor of Pathology, Ophthalmology and Oncology at Johns Hopkins. "These tumors also can suddenly become more aggressive, which we now think represents an inactivation of this tumor-suppressor gene, and this inactivity could be used as a marker to determine which patients need more therapy."

Pilocytic astrocytoma arises in brain cells known as astrocytes, which, among many functions in the brain, help support neurons. These cancerous astrocytes have DNA mutations that force a growth-related gene, BRAF, into an abnormal, always-on state. Biologists call such cancer-driving genes oncogenes.

Eberhart and his team used a viral gene-transfer technique to deliver an oncogenic, always-on version of BRAF, to fetal brain cells in a lab dish. The idea was to create a cell model of pilocytic astrocytoma, to enable easier study of its growth patterns. As the researchers expected, the cells quickly formed tumorlike colonies -- but the growth of these colonies soon sputtered out.

The same phenomenon, sparked by an oncogene, was first described six years ago in a study of the biology of skin moles. Moles typically begin in skin cells whose inherited or spontaneous mutations -- often affecting BRAF -- drive the cells' growth beyond normal limits. "The oncogene drives the excessive growth of skin cells, which forms a mole. This overgrowth triggers the downstream activation of tumor-suppressor genes, which stops the mole from growing further," says Eberhart.

In the current study, Eberhart and his colleagues found evidence that this same process, which is called oncogene-induced senescence, also occurs in pilocytic astrocytoma and minimizes its spread. As their tumor-model cells became senescent, the activity of p16, a well-known tumor-suppressor gene, increased and acted as a brake to stop further tumor growth.

Next, the researchers checked pilocytic astrocytoma samples from 66 patients, using a tissue registry at the Johns Hopkins Department of Pathology. Most (57 of 66) showed signs of p16 tumor-suppressor activity, and the remaining nine samples had no signs of p16 activity. Of the p16-active tumors, only two samples (3.6 percent) were from patients who had died of their cancer; however, three of the nine samples with inactive p16 (33 percent) were from patients who had died.

"Our hypothesis now is that these tumors become fast-growing and aggressive again when they can somehow find a way to shut off p16 and escape senescence," says Eric Raabe, M.D., Ph.D., fellow in pediatric oncology at Johns Hopkins. "In many cases, a single tumor may contain some cells that are senescent plus others that have escaped senescence and started proliferating again," he added.

In future work, Eberhart says, he and his colleagues will examine whether a new class of BRAF-inhibiting cancer drugs has the unintended side effect of shutting down p16. "Clinical trials of these BRAF inhibitors are now just starting in the U.S. and Europe," he says. "We think it's important to determine whether these drugs end up affecting the process of oncogene-induced senescence."

The study was supported by the PLGA Foundation, Children's Cancer Foundation, the Pilocytic/Pilomyxoid Astrocytoma Research Fund at Johns Hopkins Medicine, Lauren's First and Goal, St. Baldrick's Foundation Fellowship, and the Comprehensive Cancer Center, Freiburg, Germany.

Other researchers involved in the study were Kah Suan Lim, Alan Meeker, Xing Gang Mao, Deepali Jain, Eli Bar, Julia M. Kim, and Kenneth J. Cohen from Johns Hopkins; and Guido Nikkhah, Jarek Maciaczyk and Ulf Kahlert of the University Hospital, Freiburg.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Journal Reference:

  1. E. H. Raabe, K. S. Lim, J. M. Kim, A. Meeker, X.-g. Mao, G. Nikkhah, J. Maciaczyk, U. Kahlert, D. Jain, E. Bar, K. J. Cohen, C. G. Eberhart. BRAF Activation Induces Transformation and Then Senescence in Human Neural Stem Cells: A Pilocytic Astrocytoma Model. Clinical Cancer Research, 2011; 17 (11): 3590 DOI: 10.1158/1078-0432.CCR-10-3349

Cite This Page:

Johns Hopkins Medical Institutions. "Slow growth of childhood brain tumors linked to genetic process seen in skin moles." ScienceDaily. ScienceDaily, 24 June 2011. <www.sciencedaily.com/releases/2011/06/110623174132.htm>.
Johns Hopkins Medical Institutions. (2011, June 24). Slow growth of childhood brain tumors linked to genetic process seen in skin moles. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2011/06/110623174132.htm
Johns Hopkins Medical Institutions. "Slow growth of childhood brain tumors linked to genetic process seen in skin moles." ScienceDaily. www.sciencedaily.com/releases/2011/06/110623174132.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. Video provided by Newsy
Powered by NewsLook.com
Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Despite Rising Death Toll, Many Survive Ebola

Despite Rising Death Toll, Many Survive Ebola

AP (Oct. 23, 2014) The family of a Dallas nurse infected with Ebola in the US says doctors can no longer detect the virus in her. Despite the mounting death toll in West Africa, there are survivors there too. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins