It has been theorized that genetically heterogeneous tumor cell populations become mixed via gradual evolution. The CSHL team, in contrast, suggests the evolution is likely punctuated. "It's a very complicated matter to try to determine a given tumor's genetic evolution," says Hicks of the CSHL team. "The different groups of cells are geographically and anatomically intertwined. In evolutionary terms, you might think of them as distinct but intermixed 'tribes,' or subspecies. It's important to keep in mind that tumors are chaotic places. There's always a certain amount of chaotic evolution taking place, some of it reflected in rearrangement of chromosomes and some in single base-pair changes in the DNA of individual tumor cells. But our results, although based so far on a limited sample size, suggest that major clonal expansion events are relatively infrequent and may provide accessible targets for targeted treatments"
Implications for understanding metastasis
The second breast cancer sample analyzed by the team was of a single genomic type, but the team was able to determine that the liver metastasis to which it had given rise was very closely related, in genomic terms. "The data suggest the primary tumor mass formed by a single clonal expansion and that one of the cells from this event subsequently seeded the metastatic tumor, with little further evolution," according to Navin. "Although closely related, primary and metastatic tumor cells were cleanly separated, indicating to us that the two populations had not mixed" since the origin of the metastasis. Further, he noted, "differences in the pro
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory