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loss of markers on the long arm of chromosome 18 (Vogelstein et aI., 1988; Fearon et aL,
1990a). Only about II % of early stage adenomatous polyps but over 70% of carcinomas
show loss of 18q (Vogel stein et aI., 1988; Cho et aI., 1994). This suggests that DCC plays
a role in advanced adenomas. The gene is expressed in most normal tissues, including
colonic mucosa, though its expression was greatly reduced or absent in most colorectal
carcinomas (Fearon et aI., 1990a). So far, one missense mutation has been identified in the
coding region of the gene (Cho et aI., 1994). The gene encodes a 190-kD transmembrane
phosphoprotein probably a cell surface receptor involved in adhesion to an extracellular
matrix or basement membrane component (Fearon et aI., 1990a). LOH for chromosome 18q
is also seen in breast tumors (Devilee et aI., 1991a) and gastric cancer (Dchino et aI., 1992).
To date germline mutations in this gene were not observed. This might indicate that DCC
is involved in tumor progression rather than tumor initiation.
In addition to alterations in these tumor suppressor genes other changes (genes) are
frequently involved such as K-ras mutations (Vogelstein et aI., 1988), loss andlor mutations
in the p53 gene on 17p (Baker et aI., 1989; Nigro et aI., 1989; Vogelstein, 1989), loss of
22q (Okamoto et aI., 1988; Vogelstein et aI., 1989; Miyaki et aI., 1990) and loss of the
1/1I/23-Hl gene on Ip35 (Leister et aI., 1990; Cohn et aI., 1991). Loss of Ip35 was most
frequently observed in the non metastatic colon tumors (Cohn et aI., 1991). The model for
colorectal tumorigenesis as developed by Fearon and Vogelstein (1990b) is illustrated in
figure 2. One should keep in mind, however, that after the initiating APC mutation the
depicted sequence of events is by no means obligatory.
C~romOlemt:
'2p
I~ I7p
Allera~on:
GeM:
APC