Cancer of the Prostate: Molecular Genetics
195
which likely represent the early genetic
changes in prostate cancer progression.
3
Genetic Alterations in Prostate Cancer
E
v
o
l
u
t
i
o
ni
nt
e
c
h
n
i
q
u
e
sh
a
sa
l
l
o
w
e
d
more
refned
analysis
oF
somatic
genetic
changes
in
prostate
cancer
cells.
Methods
that
have
been
used
include
cytogenetic
analysis,
±ISH,
and comparative genomic hybridization
(CGH). More recently, molecular analysis
has Focused on specifc oncogenes and
tumor suppressor genes (Table 2), growth
Factors
and
their
receptors,
and
the
AR. Whereas cytogenetic analysis has
yielded important inFormation regarding
hematologic malignancies, interpretation
oF
solid
tumor
karyotypes
is
more
diFfcult.
In
addition,
prostate
cancer
Tab. 2
Genes potentially involved in prostate
carcinogenesis.
Tumor suppressor genes
N
33
MX11
P
53
RB1
DCC
Oncogenes
MYC
ERBB2
RAS
Metastatic genes
CDH1 (E-cadherin)
CTNNA 1 (
α
-catenin)
CCAM
KA11
CD44
PTEN
Androgen cascade
Androgen receptor
HSD3B2 (3
β
-hydroxysterold dehydrogenase)
SRD5A2 (5
α
-reductase)
is characterized by low mitotic rates,
tumor heterogeneity, signifcant stromal
elements,
and
poor
morphology
oF
metaphase
spreads.
Nevertheless,
the
most
common
changes
observed
are
nonrandom loss oF the Y chromosome
and
gain
oF
chromosome
7.
Others
have observed deletions oF chromosomes
7q, 8p, and 10q, as well as structural
aberrations oF chromosomes 8p22, 10q24,
and 1. These chromosomal abnormalities
were observed more Frequently in poorly
diFFerentiated, locally extensive tumors
with poor clinical outcomes. Identifcation
oF double minutes and homogeneously
staining regions, Features associated with
oncogene amplifcation, has been rare
in prostate cancer specimens. ±ISH and
CGH data have confrmed cytogenetic
fndings
and
enabled
detection
oF
additional areas oF change in prostate
cancer cells. Aneuploidy occurs in 66
to 100% oF prostate cancers. The most
common alterations include chromosome
8
(23%)
and
chromosome
7
(20%),
with involvement oF chromosomes 10,
12, X, and Y occurring less Frequently.
Aneuploid tumors demonstrated more
Frequent disease progression, most notably
with chromosomes 8 and Y, and may
have use as prognostic markers For locally
advanced prostate cancer. Chromosome 7
trisomy was noted more oFten in tumors
oF higher stage and Gleason grade. Others
have postulated
that
S-phase Fraction,
like DNA ploidy, correlates with both
pathologic Features and clinical outcomes.
However, the importance oF both DNA
ploidy and S-phase Fraction over standard
clinical
and
pathologic
inFormation
remains unclear. Comparative genomic
hybridization allows genome-wide survey
For
regions
oF
amplifcation
or
loss
by hybridizing DNA From normal and
tumor tissues with normal metaphase
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