Hopkins Geneticist Discovers Mutations in Cancer Cells

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Mon Sep 26 14:00:03 2005 Pacific Time

s Hopkins Geneticist Discovers Mutations in Cancer Cells

That Suggest New Forms of Treatment

BALTIMORE, Sept. 26 (AScribe Newswire) -- Researchers at s

Hopkins have identified three new genetic mutations in brain tumors,

a discovery that could pave the way for more effective cancer

treatments. The Hopkins team, in conjunction with researchers at the

J. Craig Venter Institute in Rockville, Md., discovered DNA

abnormalities in two tyrosine kinase proteins already known to

disrupt normal cell activity and contribute to tumor formation.

The discovery of these mutations is especially significant,

the researchers say, because tyrosine kinases can be targeted using

pharmaceuticals.

" We picked these proteins to sequence because receptor

tyrosine kinases sit on the cell surface where anticancer drugs can

get at them, " said J. Riggins, M.D., co-lead author of the

study and an associate professor in the Department of Neurosurgery at

The s Hopkins University School of Medicine.

In the study, the researchers identified two of the previously

unknown mutations in fibroblast growth receptor 1 (FGFR1) and one in

platelet derived growth factor receptor alpha (PDGFRA).

FGFR1 and PDGFRA, said Riggins, have been implicated in

several other cancers such as colorectal, breast and ovarian cancer,

as well as chronic myelogenous leukemia, gastrointestinal stromal

tumors and lymphoma.

Riggins and colleagues analyzed a catalog of 518 protein

kinase sequences taken from the Human Genome Project. Using high-

throughput gene sequencing equipment based at the Venter Institute's

Joint Technology Center, they resequenced 20 targeted proteins from

tissue samples of brain tumor cells from Hopkins. The cells came from

19 glioblastoma tumors from eight females and 11 males ranging in age

from 7 to 77 years. Glioblastomas are malignant tumors of the central

nervous system usually found in the cortex of the brain.

Researchers discovered the mutations after comparing the

resequenced genes with corresponding genes from the human genome

sequence.

A previous study by Hopkins researchers, led by Victor

Velculescu, M.D., Ph.D., used high-throughput gene sequencing to

identify 14 mutated genes that have potential links to the growth of

colon cancer cells, according to Riggins. These discoveries suggest

potential future therapies that might use small molecules and

antibodies to regulate the function of the mutated genes.

The success of that study prompted researchers to take the

same approach to search for new drug targets for glioblastoma, a

brain tumor for which current therapies are weak.

According the Riggins, the recent advances in genomic

information and technology have set the stage for the assembling of a

complete catalog of molecular alterations that contribute to cancers.

Genes involved in the tyrosine kinase family will be important in

these future studies because they play a significant role in

signaling between cancer cells and what's around them. Combined with

the remarkable clinical success doctors have had with the molecular

targeting of this family of genes, Riggins said, these new findings

could result in effective new treatments for cancer.

" The next step, " he added, " is to find inhibitors of these

mutations and find out how we can reverse the effects of these

mutations in the cancer cell. Our hope is that we can target enough

of these mutations to treat the cancer. "

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CONTACT: Vohr, s Hopkins Medicine Office of Corporate

Communications, PHONE: 410-614-5105 EMAIL: evohr1@...