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Multistep genetic changes associated with the development of colorectal cancers. Mutations in the APC gene initiate the formation of adenomas. One
sequence of mutations in an oncogene and in various tumor suppressor genes that can result in further progression to large adenomas and cancer is
indicated. Patients with familial adenomatous polyposis (OMIM 175100) inherit mutations in the APC gene and develop numerous dysplastic aberrant crypt
foci (ACF), some of which progress as they acquire the other mutations indicated in the figure. The tumors from patients with hereditary nonpolyposis
colon cancer (OMIM 120435) go through a similar, though not identical, series of mutations; mutations in the mismatch repair system (see Chapter 35)
speed up this process. K-RAS is an oncogene, and the other specific genes indicated are tumor suppressor genes. The sequence of events shown here is
Source: Cancer: An Overview, Harper's Illustrated Biochemistry, 30e
not invariable in the development of all colorectal cancers. A variety of other genetic alterations have been described in a small fraction of advanced
Citation:These
Rodwell
VW,
DA, Botham
Kennelly PJ,
Weil P. Harper's
Illustrated
Biochemistry,
30e;
2015 different
Availablecases.
at:
colorectal cancers.
may
be Bender
responsible
for the KM,
heterogeneity
of biological
and clinical
properties
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among
Instability of
http://mhmedical.com/
Accessed:
May
11,
2017
chromosomes and microsatellites (see Chapter 35) occurs in many tumors, and likely involves mutations in a considerable number of genes.
© 2017 McGraw-Hill
AllVogelstein
rights reserved
(Reproduced,Copyright
with permission,
from Bunz F,Education.
Kinzler KW,
B: Colorectal tumors, Fig. 48-2, The Online Metabolic & Molecular Bases of Inherited
Disease, www.ommbid.com)