COLORECTAL MARKER PROMISES BETTER TREATMENT By Kate Ruddon Researchers at the Medical Institutions have identified a genetic marker for colorectal cancer that could improve survival rates by helping physicians determine which patients are candidates for postoperative therapy. The findings were reported in last week's New England Journal of Medicine. Over the last 10 years, Hopkins researchers have discovered multiple genetic alterations responsible for the development and progression of colorectal cancer. One of those alterations--the loss of the long arm of chromosome 18- -frequently occurs late in the progression of colorectal cancer and appears to play a role in accelerating the spread of the cancer and making it more lethal. Researchers believe the inactivation of tumor suppressor genes, including the DCC gene, located on this region of chromosome 18, may be responsible for these events. This new study shows that loss of the long arm of chromosome 18 is an effective marker of patients who may benefit from treatment with drug and radiation therapy following surgery. The team from the Hopkins departments of Oncology and Pathology studied the tumors of 135 patients with stage II and III colorectal cancers, using a technique called polymerase chain reaction, or PCR, to amplify, more than a million times, a fragment of DNA. They examined chromosome 18 to see if the loss of the long arm was a prognostic marker for the disease. The investigators found that among patients with stage II disease who had retained both unaltered copies of chromosome 18, the five-year survival rate was 93 percent. Among patients who were missing a copy of the long arm of chromosome 18, the five-year survival rate declined to 54 percent. Survival among patients with stage III disease did not change significantly. "These findings tell us that chromosomal loss may be an important prognostic marker in stage II colorectal cancer," said Stanley Hamilton, professor of pathology and oncology and lead investigator in the study. "Analysis of the chromosomal status in tumors is a new source of information that has a substantial impact on patient survival in higher risk groups." Physicians currently determine which patients should receive postoperative therapy based mainly on the pathological staging of the disease. The new information indicates that colorectal cancer patients who are missing the long arm of chromosome 18 in stage II tumors are more likely to die of their cancers and therefore may benefit from drug and radiation therapy. Those patients who have retained both unaltered copies of the chromosome could be spared additional therapy after surgery. More than 150,000 people in the United States are diagnosed with colorectal cancer each year. As many as 60,000 die each year from the disease. The research at Hopkins over the past decade has led to diagnostic markers and screenings that are expected to greatly improve survival. Other participants in the research are Jin Jen, Hoguen Kim, Steven Piantadosi, Zong-Fan Lieu, Roy C. Levitt, Pertti Sistonen, Kenneth W. Kinzler and Bert Vogelstein.
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