Seattle, WA--Can distinctive changes in DNA structure be seen before cancer tumors begin to grow? Can tumor metastasis be predicted by observing particular DNA alterations in cells? The answer to both of these questions, according to two recent studies by scientists at the Pacific Northwest Research Institute (PNRI, now PNDRI), appears to be yes.

This week's issue of the Journal of the National Cancer Institute (JNCI) highlights two new papers from the Biochemical Oncology Program at PNRI. The papers describe cancer phenotypes that are detectible in normal cells before the appearance of primary tumors and before any evidence of metastasis. According to Dr. Donald Malins, lead author of the studies, "early detection is one of the most important tools we have against cancer. To be able to find evidence for a metastasizing tumor before it begins to metastasize would be a very powerful new weapon in the care of cancer patients."

In the first of the two papers, both published this summer in Proceedings of the National Academy of Sciences, Malins and his colleagues demonstrate that distinctive structural changes can be detected in the DNA of normal cells well before the growth of any primary tumor. In the following paper, they show that different structural changes can be seen in the DNA of normal cells before tumor metastasis has begun. In both cases, the structural changes are so distinctive that they form what Malins calls a cancer phenotype.

The phenotypes Malins and his colleagues have discovered are visible through a sophisticated technology called Fourier transform-infrared (FT-IR) spectroscopy . Using this technique, researchers can see that the DNA changes of tumor cells are structurally indistinguishable from the DNA of normal cells surrounding the tumor. Further, they can see the tumor phenotype in normal cells even before the primary tumor begins to grow.

In a similar way, the FT-IR technology can distinguish the DNA changes of metastatic tumors from those of primary tumors. The two phenotypes are in fact so markedly different that they call into question the conventional view of metastasis. As Malins puts it, "the current concept of metastasis is, if not wrong, at least not entirely correct."

In her report on these results, Karyn Hede of the JNCI explains how Malins' work provides new evidence for the view that metastatic cells are fundamentally different from primary tumor cells. "Rather than beginning," Hede says, "as primary tumor cells that somehow acquire the ability to become invasive and mobile," metastatic cells may develop through an entirely independent process. Primary tumor cells and metastatic tumor cells may, in other words, be "hardwired" differently. And this possibility has important implications for our understanding of the growth and development of cancer as well as for possibilities of treatment and prevention. For further information, contact Donald C. Malins, PNRI, 206-726-1240, dmalins@pndri.org.