Evidence Found for viral Basis of Tumors

Harvard researchers at the Dana-Farber Cancer Institute have found evidence of a viral basis for brain tumors, according to a recent study published in the New England Journal of Medicine.

Associate Professor of Pediatrics Dr. Robert L. Garcea '70 reported last week in the Journal that he and colleagues at the Institute have correlated DNA sequences in pediatric brain tumors and in simian virus 40 (SV40).

SV40 is known to lead to tumors in certain animals, including humans. The rare tumors associated with the virus usually appear before two years of age in humans, and doctors often have difficulty treating them because they lie deep within the brain, in an area known as the choriod plexus, which manufactures cerebro-spinal fluid.

Garcea said in an interview yesterday that past research has implicated a protein, called a t-antigen, in all choriod plexus tumors in laboratory animals. The t-antigen has been shown to result from the expression of an SV40 DNA sequence.

Past research by other doctors has linked the activity or antigens, foreign substances against which the body's immune system acts, to the expression of DNA sequences called oncogenes, which eventually lead to cancer.

The pediatrician said that early use of transgenic mice, into whose gametes the sequence coding for the t-antigen was inserted, led to the conclusion that SV40 was involved when all of the animals developed the tumors.

Eventually, using DNA probing techniques on 31 pediatric tumor samples, Garcea showed that a large fraction of the samples reacted with the sequence for the SV40 t-antigen.

Eventually, Garcea said, he hopes to verify the finding with more samples. However, because of the rarity of the disease--only a few hundred cases are diagnosed each year in the U.S.--it will be difficult to locate enough samples for such a study, he said.

But, Garcea said, the study's publication may bring more such cancer victims out of the woodwork for further projects. "We want to accumulate as many samples as possible," he said. "If the finding holds up, the next logical stop is a histological study of fetal serum."

Garcea emphasized that further study on the tumors was necessary.

"I think people are very skeptical about viral links to cancer," he said. "It's a controversial area."

Fruit Fly Protein Is Clue to Embryo Growth

Scientists may be one step closer to unravelling the complex path of the human embryo's development form the joining of sperm and egg to birth, thanks to a team of researchers at Boston Children's Hospital.

This month's issue of Nature Genetics features an study by Fikes Professor of Pediatric Medicine Dr. stuart H. Orkin and several colleagues, who have deduced remarkable similarities in amino acid sequence between a human gene expression regulator, CCAAT displacement protein (CDP), and the cut protein, an important regulator of cell differentiation in fruit flies (Drosophila).

Both of these proteins had been shown to be active in the development of their respective organisms. Dr. David G. Skalnik of the Indiana University School of Medicine, a co-author of the paper, had in earlier work found evidence linking CDP the maturation of human white blood cells.

The cut protein is one of a family of similar proteins, called homeoproteins, found across species which control development. Mutations of the protein's structure have been implicated in a number of mutations in many regions of the fruit fly.

For instance, said Instructor in Pediatrics Dr. Ellis J.Neufeld, another co-author of the study, in one mutation of the cut gene, neurons in the front edge of the fruit fly wing do not develop, and the wing appears "cut." hence the name.

There is precedence for conservation of protein sequences with similar function between species, Neufeld said. The fact that the CDP protein has now been located in every mammalian cell that has been examined could mean that the protein serves as widespread a role in human development as the cut protein does in Drosophila.

It is thought that the action of CDP is an inhibitory one. If the proteins involved in white blood cell differentiation are bound by CDP, maturation will not take place. However, once maturation takes place, Neufeld said, CDP no longer binds.

The cut protein is also believed to act in an inhibitory fashion. This similarity, along with the fact that both proteins do not act in a specifically positional way, said Neufeld, give more evidence to support a relation in function to the two proteins.

Neufeld said that the group would next be studying the specific action of CDP in order to better construct a mechanism of action in development.

"Our focus is proving it is a repressor, and to understand what the gene has to do with control of the white blood cell," he said. "We hope to use the white blood cell as s model system and also to use it to understand what [CDP] does in early development."

A Little Bit Closer Now

Most of us wouldn't get that excited about coming a few thousandths of a percentage point closer to a goal. If the federal government prided itself on cutting the national deficit by that much, for instance, there'd be a news story every time Congress cut a million dollars from its budget.

But scientists seem to need more reassurance. An article in this month's genetics supplement to Nature, a well-respected weekly British science journal, reports in a headline, "Genome Project; Another 0.003 Percent Completed."

The huge advance, part of a $3 billion, 15-year project to identify all the sequences of DNA in the human genome, was made by National Institutes of Health researcher Craig Venter.

Venter and colleagues have identified 100,000 more base pairs in the human DNA sequence. To be sure, this entails quite a few hours in the laboratory, but compared to the whole genome--which is thought to consist of approximately three billion base pairs--it's not much.