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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 chromosomal locations of the
Source: Chapter 55. Cancer: An Overview, Harper's Illustrated Biochemistry, 29e
various genes shown here are known. The sequence of events shown here is not invariable in the development of all colorectal cancers. A variety of other
Citation:
Murray
Bender in
DA,
Botham
KM, Kennelly
PJ, Rodwell
VW,
Weil P.These
Harper's
Illustrated
Biochemistry,
2012 Available
at:
genetic alterations
have
beenRK,
described
a small
fraction
of advanced
colorectal
cancers.
may
be responsible
for the 29e;
heterogeneity
of biological
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May
11,
2017
and clinical properties observed among different cases. Instability of chromosomes and microsatellites (see Chapter 35) occurs in many tumors, and likely
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involves mutations
in a ©considerable
numberEducation.
of genes. All
(Reproduced,
with permission, from Bunz F, Kinzler KW, Vogelstein B: Colorectal Tumors, Fig. 482, The Online Metabolic & Molecular Bases of Inherited Disease, www.ommbid.com)