Navigation Links
Slow growth of childhood brain tumors linked to genetic process 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.

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."


Contact: Vanessa Wasta
Johns Hopkins Medical Institutions

Related medicine news :

1. Scientists image beginning stages of ovarian cancer growth with time-lapse technique
2. Cancer cells accelerate aging and inflammation in the body to drive tumor growth
3. Common transplant drug inhibits breast cancer growth, UNC laboratory study shows
4. Enzyme may drive breast cancer growth
5. Artificial tissue promotes skin growth in wounds
6. Obstructive sleep apnea linked to cancer growth in mice
7. Rapid growth may be appropriate trigger for treatment in patients with renal masses
8. Increases in peripheral arterial disease revascularization correlates with screening growth
9. Extra Sleep in Infants Seems to Signal Growth Spurts
10. Study is the first to link sleep duration to infant growth spurts
11. In time for spring, biologist illuminates how seedlings regulate growth
Post Your Comments:
(Date:11/24/2015)... ... November 24, 2015 , ... Brillouin Energy ... Brillouin is the developer of renewable energy technologies capable of producing commercially useful ... announced today that its WET™ and HHT™ Boiler System reactor core modules were ...
(Date:11/24/2015)... , ... November 24, 2015 , ... ... the United States to support their local poison centers through donations on Tuesday, ... #GivingTuesday: calls it “a day that inspires people to collaborate in improving ...
(Date:11/24/2015)... ... , ... Aided by seed funding from the Ron Foley Foundation, researchers at ... into how to detect and treat pancreatic cancer (PC). , WCHN researchers will ... molecules (ncRNA), genetic material that is present in the blood of patients with PC. ...
(Date:11/24/2015)... ... ... Willey , has answered a new calling – to relieve snoring and sleep apnea for ... and sleep apnea through oral appliance therapy. He is one of a number ... of four in the Illinois area. , Dr. Willey’s location is at 11825 ...
(Date:11/24/2015)... ... , ... Autism Speaks, the world’s leading autism science and advocacy organization, will ... generosity of people around the world. On December 1, supporters can make an online ... share the personal stories behind those gifts. , Just as Black Friday and ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... The hope of bearing a ... IVF cycles. After failure of over 15 IVF cycles, ... all hopes that she would be able to conceive ever. But finally optimism prevailed as ... failure of over 15 IVF cycles. ... take one last attempt with Gaudium IVF Center in ...
(Date:11/24/2015)... CARLOS, Calif. , Nov. 24, 2015 ... a leader in non-invasive genetic testing and ... announced that it will present at the ... in New York on Wednesday, December 2, 2015 at 1:00 p.m. ET.  Matthew ... the Company,s financial results, business activities and ...
(Date:11/24/2015)... 2015 /PRNewswire/ - ESSA Pharma Inc. ("ESSA" or the ... that the first patient has been enrolled in ESSA,s ... for metastatic castration-resistant prostate cancer ("mCRPC"). ... --> the United States and ... clinical trial, ESSA intends to demonstrate the safety, tolerability, ...
Breaking Medicine Technology: