Johns Hopkins Gazette: August 8, 1994

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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