CHAPTER X CHAPTER 4 - Cancer et environnement

A
B
Fig. 4.03 Germ cell tumours genetics. A Example of G-banding of chromosomes 12 (left) and an isochromosome 12p (i(12p), right) isolated from a primary non-seminoma
of the adult testis. B Schematic representation of a normal chromosome 12 (left) and an i(12p) (right). C Representative example of fluorescent in situ hybridization
on an interphase nucleus of a cell line derived from a primary non-seminoma of the adult testis. The centromeric region of chromosome 12 is stained in red,
while part of 12p is stained in green. Note the presence of three normal chromosomes 12 (paired single red and green signals, indicated by an arrow), and two
i(12p)s (paired single red and double green signals, indicated by an arrowhead).
C
Karyotyping, FISH, CGH and spectral
karyotyping (SKY) {388-390,1360,1794,
1854,1988,2217,2535,2692} revealed a
complex but highly similar pattern of
over- and underrepresentation of (parts
of) chromosomes in seminomas and nonseminomas.
Parts of chromosomes 4, 5,
11, 13, 18 and Y are underrepresented,
while (parts of) chromosomes 7, 8, 12
and X are overrepresented. Seminomas
have significantly more copies of the
chromosomes 7, 15, 17, 19, and 22,
explaining their higher DNA content
{2235,2692}. This supports a common
origin of all histological subtypes of these
tumours, in accordance to findings in
TGCTs, composed of both a seminoma
and a non-seminoma component {388,
880,2250}.
mal aberration in invasive TGCTs is gain
of 12p-sequences, most often as i(12p)
{2290}, for review. The i(12p) was initially
reported in 1982 by Atkin and Baker
{129,130}, and subsequently found to be
characteristic for TGCTs [{1743}, for
review]. Molecular analysis showed that
the i(12p) is of uniparental origin {2428}
indicating that its mechanism is doubling
of the p-arm of one chromosome, and
loss of the q-arm, instead of non sister
chromatin exchange {1827}. Interestingly,
i(12p) is not restricted to the seminomas
and non-seminomas of the testis,
but is also detected in these types of
tumours in the ovary, anterior mediastinum
and midline of the brain. The
majority of TGCTs, up to 80%, have
i(12p) {2692}, while the remaining cases
also show additional copies of (part of)
12p {2216,2529}. This leads to the conclusion
that gain of 12p-sequences is
Table 4.04
Summary of the investigated proto-oncogenes studied for their involvement in the pathogenesis of TGCTs.
The candidates are classified based on the supposed biological pathway. Their chromosomal localization
is indicated, as well as the references.
(Putative) pathway Gene Chromosomal
localization
Reference(s)
Overrepresentation of 12p and
candidate genes
The only consistent structural chromoso-
Cell cycle control
CCNB
CCND2
CCNA
CCNE
5q12
12p13
13q12.3-13
19q1
{175}
{174,1128,2325,2436}
{175}
{175}
Cell survival/
apoptosis
c-KIT
FAS
DAD-R
MDM2
TCL1
4q12
10q24
12p11.2
12q14-15
14q32.1
{2135,2517,2518,2615}
{2557}
{2914}
{1301,2199}
{1869}
Translation
E1F3S8 16p11.2 {2251}
Transcription
MYCL1
MYCN
MYBL2
1p34
2p24
20q13
{2436}
{2436}
{2436}
Fig. 4.04 Teratoma of the adult testis. Fluorescent
immunohistochemical detection of centrosome
hypertrophy on a histological section. The centrosomes
are stained in red, and the nuclei are counterstained
in blue (DAPI). Normal centrosomes are
indicated by an arrow, and hypertrophic centrosomes
by an arrowhead.
Signalling
Stem cell biology
Unknown
RHOA
KRAS2
GRB7
JUP1
3p21
12p12
17q11
17q11
HIWI 12q24 {2123}
POV1 11q12 {2436}
{1262}
{834,1829,1953,2192,2436}
{2436}
{2436}
Germ cell tumours
225