Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CANCER AS A MICROEVOLUTIONARY PROCESS
1093
cancers of
epithelia:
carcinomas
oral cavity
and pharynx
digestive
organs
respiratory
system
breast
reproductive
tract
urinary
system
skin melanoma
blood: myelomas, leukemias,
and lymphomas
nervous system
bones, connective tissue,
muscles, and vasculature
endocrine system,
thyroid
other
KEY:
new cases
deaths/year
0 100 200 300
number per year (thousands)
Figure 20–2 Cancer incidence and
mortality in the United States. The total
number of new cases diagnosed in 2012
in the United States was 1,665,540, and
total cancer deaths were 585,720. Note
that deaths reflect cases diagnosed at
many different times and that somewhat
less than half of the people who develop
cancer die of it. In the world as a whole, the
five most common cancers are those of the
lung, stomach, breast, colon/rectum, and
uterine cervix (included in the figure under
the heading of reproductive tract), and the
total number of new cancer cases recorded
per year is just over 6 million. Skin cancers
other than melanomas are not included in
these figures, since almost all are cured
easily and many are unrecorded.
The data for the United Kingdom are
similar. However, incidences are different
in some other parts of the world, reflecting
widespread exposures to different
infectious agents and environmental toxins.
(Data from American Cancer Society,
Cancer Facts and Figures, 2014.)
Most Cancers Derive from a Single Abnormal Cell
Even when a cancer has metastasized, we can usually trace its origins to a single
primary tumor, arising in a specific organ. The primary tumor is thought to derive
by cell division from a single cell that initially experienced some heritable change.
Subsequently, additional changes accumulate in some of the descendants of this
cell, allowing them to outgrow, out-divide, and often outlive their neighbors. By
MBoC6 m20.02/20.02
the time it is first detected, a typical human cancer will have been developing for
many years and will already contain a billion cancer cells or more (Figure 20–4).
Tumors will usually also contain a variety of other cell types; for example, fibroblasts
will be present in the supporting connective tissue associated with a carcinoma,
in addition to inflammatory and vascular endothelial cells. How can we
be sure that the cancer cells are the clonal descendants of a single abnormal cell?
One way of proving clonal origin is through molecular analysis of the chromosomes
in tumor cells. In almost all patients with chronic myelogenous leukemia
(CML), for example, we can distinguish the leukemic white blood cells from
the patient’s normal cells by a specific chromosomal abnormality: the so-called
Philadelphia chromosome, created by a translocation between the long arms of
chromosomes 9 and 22 (Figure 20–5). When the DNA at the site of translocation
is cloned and sequenced, it is found that the site of breakage and rejoining of the
translocated fragments is identical in all the leukemic cells in any given patient,
but that this site differs slightly (by a few hundred or thousand base pairs) from
one patient to another. This is the expected result if, and only if, the cancer in each
patient arises from a unique accident occurring in a single cell. We will see later
lumen
basal lamina
normal duct benign tumor malignant tumor
Figure 20–3 Benign versus malignant
tumors. A benign glandular tumor (pink
cells; an adenoma) remains inside the basal
lamina (yellow) that marks the boundary
of the normal structure (a duct, in this
example). In contrast, a malignant glandular
tumor (red cells; an adenocarcinoma) can
develop from a benign tumor cell, and
it destroys the integrity of the tissue, as
shown. There are many different forms that
such tumors may take.