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Tracking translocations

Beyond their appearance under the microscope, sarcomas are characterized by peering into their "heart and soul," the chromosomes that hold their genetic programming. Jonathan Fletcher, MD, who holds appointments at Dana-Farber, Brigham and Women's, and Children's Hospital Boston, is a master of this "cytogenetic" approach to tumor classification.

"When a sarcoma is surgically removed or biopsied, we take a sample, work it into individual cells, and grow them in the lab," explains Fletcher (no relation to Christopher). "When they're dividing rapidly, we look at their chromosomes under the microscope." Fletcher's quarry are "translocations," instances where chromosomes have broken apart and reconnected at the wrong places. Specific translocations can help doctors diagnose different types of sarcomas, but Fletcher and his colleagues are also interested in finding genes that have been wrenched from their accustomed place on the chromosome and relocated elsewhere.

"Identifying those genes and determining what role they play in normal and cancer cells provides us with targets for new treatments," says Fletcher. His research group also focuses on kinases, proteins that signal the normal or cancerous behavior of cells. Through an elaborate procedure, Fletcher and his colleagues can isolate virtually every form of a class of "tyrosine kinases" produced by sarcoma cells, and identify those that make the most inviting candidates for therapeutic attack.

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