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Title
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Characterization of human colon cancer antigens recognized by autologous antibodies.
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Authors
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M.J.Scanlan,
Y.T.Chen,
B.Williamson,
A.O.Gure,
E.Stockert,
J.D.Gordan,
O.Türeci,
U.Sahin,
M.Pfreundschuh,
L.J.Old.
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Ref.
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Int J Cancer, 1998,
76,
652-658.
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PubMed id
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Abstract
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The screening of cDNA expression libraries derived from human tumors with
autologous antibody (SEREX) has proven to be a powerful method for defining the
structure of tumor antigens recognized by the humoral immune system. In the
present study, 48 distinct antigens (NY-CO-1-NY-CO-48) reactive with autologous
IgG were identified by SEREX analysis in 4 patients with colon cancer.
Sequencing analysis showed that 17 of the cDNA clones were previously
uncharacterized molecules and 31 represented known gene products. The individual
cDNA clones were analyzed in the following manner: a search for mutations or
other structural changes; an analysis of mRNA expression in a panel of normal
tissues; and a frequency analysis of the antibody response to the expressed
product in the sera of colon cancer patients and normal individuals. The initial
analysis showed NY-CO-13 to be a mutated version of the p53 tumor suppressor
gene. Three of the 48 antigens showed a differential pattern of mRNA expression,
with NY-CO-27 (galectin-4) expressed primarily in gastrointestinal tract, and
NY-CO-37 and -38 showing a pattern of tissue-specific isoforms. With regard to
immunogenicity, 20 of the 48 antigens were detected by allogeneic sera; 14 of
these were reactive with sera from both normal donors and cancer patients, and 6
other clones (NY-CO-8, -9, -13, -16, -20 and -38) reacted exclusively with sera
from colon cancer patients (ranging from 14% to 27%). Our results on colon
cancer illustrate both the complexity and the potential of the SEREX approach
for analysis of the humoral immune response against human cancer.
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