s Hopkins Geneticist Discovers Mutations in Cancer Cells That Suggest New Forms of Treatment

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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. "