[CANCER RESEARCH 49. 5696-5701. October 15. 1989]
Chromosomal Changes in Human Primary Testicular Nonseminomatous
Tumors1
Sergio M. M. J. Castedo,2 Bauke de Jong,' J. VV'olterOosterhuis,
Germ Cell
Raquel Seruca, Vera J. S. Idenburg, Anke Dam,
Gerard te Meerman, Heimen Schraffordt Koops, and Dirk T. Sleijfer
Departments of Human Cenelics fS. M. M. J. C.. B. tie J., R. S., G. J. le M.¡,Pathology [J. ». O., A. lì.].Surgical Oncology ///. .V. A'./, and Medical Oncology
[D. T. S.], State L'niverxity of Groningen, Antonias Deusinglaan 4, 9713 A H Groningen. The .\etherlands
ABSTRACT
A cytogenetic analysis uf 14 primary testicular nonscminomatous germ
cell tumors has been carried out after short term tissue culture. The
modal chromosome numbers ranged from 53 to 113, in agreement with
flow cytometric determination of the DNA content of the tumors. At least
one copy of an i(12p) was present in 12 tumors. IMO tumors, however,
lacked that marker. Some chromosomes are apparently overreprcsented,
whereas others are underrcpresented, although some differences between
seminomas and nonseminomas were noticed.
INTRODUCTION
Testicular germ cell tumors of adults can be divided both
clinically and morphologically in two distinct entities, seminoma and nonseminomatous germ cell tumor (1-3). The latter
may have one or more of the following histológica! subtypes:
embryonal carcinoma; teratoma; yolk sac tumor; and choriocarcinoma. In the British classification (4) tumors with a seminoma and a NSGCT4 component are classified as combined
tumors; in the WHO classification they are classified as
NSGCT (3). In about 20% of germ cell tumors seminoma and
NSGCT coexist (4, 5). In general, seminomas are less aggressive
than NSGCT, although the aggressiveness of the latter depends
on the histológica! subtype, in particular the presence of em
bryonal carcinoma, yolk sac tumor, and/or choriocarcinoma.
From the different theories on the pathogenetic relationship
between seminomas and NSGCT (2, 6-12) two main concepts
emerge. One model updates the former hypotheses of Pierce
and Abell (8) and assumes that seminomas and NSGCT inde
pendently derive from transformed (dysplastic) intratubular
germ cells via carcinoma in situ (2, 10, 11). Another model
suggests that all testicular germ cell tumors (with the possible
exception of spermatocytic seminoma) have a single origin in
carcinoma in situ and progress through a seminoma stage (9,
12). This hypothesis represents a further development of the
theories of Ewing (6) and Friedman (7).
Cytogenetic studies of seminomas and NSGCT, as well as of
the seminoma and NSGCT components of combined germ cell
tumors of the testis, may clarify the possible relationship be
tween the different subtypes of testicular germ cell tumors.
Recently, we presented our cytogenetic findings in semino
mas (13) and in a combined germ cell tumor of the testis (14).
Now we report the results of the cytogenetic analysis and
DNA flow cytometry of 14 primary NSGCT.
described (15). For chromosome preparations the tumor cells were
harvested after short term tissue culture (on an average of up to 7 days),
either by brief trypsinization or according to the procedures described
by Gibas el al. (16). Colcemid (0.05-0.5 pg/m\ culture medium) was
added 2 to 5 h before harvesting. After harvesting, the cells were
centrifuged for 5 min at 240 x g. The pellets from the trypsinized cells
were resuspended in 0.06 M KOI. incubated at 37°Cfor 15 min,
centrifuged, resuspended in a mixture of methanolracctic acid (3:1),
centrifuged. resuspended, and left in the tubes for 20 min. The pellets
from the cells harvested as described by Gibas et al. were immediately
resuspended in fixative. In both methods there was a final centrifugation, after which the cells were resuspended and pipeted onto slides.
Air dried chromosome preparations were GAG and/or GTG banded.
In addition, tumor 12 (combined tumor) was dissected in order to
separate the seminomatous and nonseminomatous components. Cells
from the seminoma component were then directly harvested for chro
mosomal study (17).
For a statistical evaluation of the chromosomal findings, the number
of normal copies per chromosome was analyzed for 14 cases with a 2way analysis of variance. The modal chromosome numbers of this series
of NSGCT and of our series of seminomas ( 13) were compared using
the Mann-Whitney U test.
Clinical staging was carried out as described by Peckham et al. (18).
RESULTS
A summary of the clinical, histopathological, and cytogenetic
data of all cases is given in Table 1.
Karyotypes. The karyotype of one metaphase from each case,
representative for the clonal structural abnormalities observed,
is described in Table 2. An overview of the numerical abnor
malities found in all cases is presented in Table 3. Figs. 1-4
show karyotypes of, respectively, cases 3, 9, 10, and 14. Case
12, cases 2 and 11, and case 7 have been described previously
(14, 19, 20).
Statistical Analysis. The analysis of variance showed that all
effects are highly significant, indicating that copies of normal
chromosomes are present in different numbers and that differ
ent tumors have different total numbers of chromosomes. The
interaction term, which is used as error term, is numerically
rather small. The variability is best described by saying that
some tumors have more chromosomes than others and that
some chromosomes are found in higher numbers than others.
The distribution of the numbers of copies of chromosomes does
MATERIALS AND METHODS
not vary very much depending on the person whose cells are
The tumors were submitted fresh and sterile at the time of diagnosis.
analyzed.
Tissue culture and DNA flow cytometry were carried out basically as
Fig. 5 shows the mean chromosome counts combined for all
cases, after standardizing the total number of normal chromo
Received 6/13/88; revised 1/13/89. 5/22/89: accepted 7/5/89.
The costs of publication of this article were defrayed in part by the payment
somes to the arbitrary number of 46. Multiple comparison
of page charges. This article must therefore be hereby marked advertisement in
using the Newman-Keuls method shows that the normal copies
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
' This work was supported by Grant GUKC 84-06 of the Netherlands Cancer
of chromosomes 12 and X are more frequently found than the
Foundation (KWF). by the Jan Kornelis de Cock Stichting. and by an institutional
numbers of copies of normal chromosomes 1, 2, 5, 9, 10, 11,
grant from the Hubrecht Laboratorium. Utrecht. The Netherlands.
* Member of the staff of the Department of Medical Genetics, Medical Faculty
13, 14, 15, 18, 19, 22, and Y.
of Oporto. Portugal.
The modal chromosome numbers of NSGCT are significantly
1To whom requests for reprints should be addressed.
' To abbreviation used is: NSGCT. nonseminomatous germ cell tumor.
lower than those of seminomas (P < 0.05).
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CYTOGENETICS.
Table
1 Summary
PLOIDY. AND PATHOGENESIS
of the clinical, histopathological,
OF NSGCT
anil cytogenetic
dala of the 14 cases
DNA
of metaphases
stage"I1IVI11IVIIICIIICIVIV1Histology
analyzed*12971575249910971113Modal
ofindexEC/T1/TD/CHO'EC/TI/TDEC/YSTDEC/TD/TIEC/TD/YSEC7TI/TD/YSTI/TDECEC/TD.45.27'.27(1.26)''.45.59(1.42).27!.26.2
Primary NSGCT
Case123456789KlII\21314Patient
age(yr)19241924142223232364242431Clinical
no.65555765645911)257596(153'10
1.33SE/EC
SE: 1.68, NSE:
SE:2.51,NSE:2EC/TI/TD/YS
1.29EC/TI/TDAS
2.43(1.47)No.
" At presentation [according to the report of Peckham et ai. ( 18)].
* Numbers refer only to abnormal metaphases.
c EC, embryonal cell carcinoma: CHO. choriocarcinoma; TI, immature teratoma; TD. mature teratoma: YS. yolk sac tumor; SE. seminoma; NSE, nonseminomatous
component. The SE and NSE components of the tumors 11 and 12 «ereseparately processed for DNA flow cytometry.
**Numbers in parentheses, secondary stemlines.
(' No metaphases were obtained from the seminoma component.
f Average chromosome number of } metaphases from the seminoma component: 126.
Table 2 Karyotypical
Case
1
2
3
4
5
6
7
8
9
10
11
12
13
14
description
of a representative
metaphase
from each case
Karyotype
12,+ 12.- 13.+ 15.+ 15.+ 17.+20.+2 1.+2 1.+dcr(6)t(6:?)(p25:?).+i( 12p).+i( 12p).+mar 1( 1qter-^q 11::?).
66.X Y.+X.+ 1.+4.+7,+7,+8,+8,+
+mar2.+mar3.
55,X Y.+6.+7.+7.- 11,+ 12,+der(2)t( 1;2)(p32:q35).+dcr(3)l(3:4?)(pl 1:pl 1?),der(8)t(8:?)(q24;?),+der( 11)t( 11:?)(q25;?),+der( 17)t( 17:?)(p 11;?),
+der(21)t(l;21)(ql2;pll).
57.X Y.+X.+ 1,+2,+7,+ 12.- 14.-20.+2 1,+del(7)(q32),+i( 12p).+i( 12p).+der( 13)t( 13: 14)( I 3qter->p 11::14q 11-K)3 1).+del( 17)(p 11),+mar I . +mar2.
64.X Y.+X.+X,+2,+3.+4.+6.+7.+8.11,+ 12,+ 14,+ 16,+ 17,+2 1,+der( 1)t( 1; 11)(p34;q 13).+der( 11)t( 1; 11)(q 12;q23).+i( 12p).+i( 12p),+i( 12p),
+mar(der(7)?).
64.\Y.+X.+X.+X.-l,+2,-H3,+6,+7,+
12,-14,-15,+16,+
17,+ 18,+21,+21,+22,+del(l)(p35).+del(l)(p35).+der.(8)t(8:?)(q24:?),+i(12p),+i(12p),
+i( 12p).+der( 15)t( 15:?)(pl 1:?).
59,XY,+inv(X)(pll.2p22.1).+Y,+3.+6.+
ll.+ 12,-H6,+ 17.+der(8)t(8:?)(q24;?),+i(12p).+i(12p),-(-i(12p),+mar(lqter-K)ll::?).
102.XX YY,+X.+X.+3.-5.-6.-7.-7.+8.-9.10,- 10,- 11,- 11.- 11,- 16,- 17,- 19.+20,-22.-22,-22,+der(
1)[comparedt( 1;?)(p 13:?).+dcl(3)
(p23),+der,(5)t(5;?)(q3 1:?),+del(6)(q2 1).+der(7)t(7;7)(p 15;q 11),+inv(7)(p 15p22),+del(8)(p 12).+del(9)(p 11).+del( 10)(pl 3). with 4n].+der
( 11)t( 11:14)(q 14;q 11),+der( 11)t( 11:?)(q25;?),+del( 12)(q 15q24),+del( 12)(q 15q24).+i( 12p).+i( 12p).+i( 12p).+i( 12p),+i(22q).+i(22q),+mar 1
(der(7)?).
59.X Y,+X,+2,+6,+8,4- 12,4-15,+ 16,+ 17,+20.+del( 1)(p2 1).+i( 12p),+i( 12p).+i( 12p). |also clonal: der( 1)t( 1;I )(p22;q2 1))
59,X,Y.+X.+ Y.+7.+8.- 11.+ 12.+ 14.+20.+der( 1)t( 1:?).(p 11:?),+del(2)(q3 1).+i( 12p),+i( 12p).+ i(12p),+der( 14)t( 14;?)(q24:?).+der( 17)t
(17;?)(q25:'.'). (also another clone with a del(l)(p34 q42). and without the der(l) and the der(14)].
60,X,-Y,+X,-2,+3,-4,+7,+8,-t-8.11.+ 12,+ 14,+ 17.+20.+20.+2 1.+21.+2 1,+22.+der(2)t(2;?)(p23;?),+dup(4)(q 12-K)2 1).+der( 11)t( 1; 11)
(qll;q21 or q23-24).+i(12p).
53,X.-Y.+der(X)t(X:?)(p 11:?),- 1,-3,-3,-6,+8,+
12.- 14,- 18,-2 1,-2 1,-22,+der( 1)t( 1:?)(p35 or 36:?).+der( 1)t( 1:?)( 1q32—p35 or p36::7),
+del(l)(ql2).+del(2)(q34).+der(3)t<3:3)(q21:q27).+del(3)(q21).
+der(3)t(3;7:3?)(3qter-»p21::7q36—*)1 I::3q25?^qter?),+del(5)(pl
1 or pl2).
+dic(7)t(7; 17)(q3 1;p 13).+der( 14)t( 12: 14)(q 13;p 11).del(20)(q 12),+der(2 1)t(2 1:22)(p 11:q11).+mar.
104.XX YY.+X,- 1,- 1,-2,+3,-4,-5,-8,-9,10,- 15.- 15,+ 17.+20.+2 1,+2 1,-22,+inv( 1)(p32q2 1).+i( 1p),+i( 1p),+der(2)t( 1:2)(q 12q37),
+der(2)l( 1;2)(q 12;q37),+del(7)(p22).+del(7)(p22),+del(7)(q22),+der(8)t(8;9)(p23;ql
2).+der(8)t(8;9)(p23;ql 2),+i( 12p),+i( 12p),+i( 12p),
+i( 12p),+der( 15)t( 15;?)(p 11;?).+mar 1,+mar2.
60.X Y.+X.+3.+7.+8.+ 12.+1 7.+20.+2I ,+der( 1)t( 1;?)(q2 1:?).+i( 12p).+i( 12p).+i( 12p).+i( 12p).del(22)(ql 2).
113.XX YY.+der(7)t(7;?)(q 11;?).+der(8)t(8:?)(p2 1:?).+der( 11)t( 11:?)(q23:?).+i( 12p).+i( 12p).+der( 14)t(7; 14)(q2 1:p 12).+der( 19)t(7; 19)(q2 1:p 13).
+dic(20)t( 1:20)(q44:p 13).
Table 3 Modal number of normal chromosomes and ¡(I2p)per case
Modal no. of normal copies of chromosomes/tumor
No. of
<^ase1234567891011121314Total132321422212243222233343212325373322333
¿pj2023334331044234
522305344042T232422123233253222232322324346232333
33221425387443332233243543842232533433354492222232222324321022222222223.52431.511212123221123.52327.5124
433335364913222224222242535142213242331425361532222432222243416222333
322233243617322333
333324.53542.51822222422213243219222223222242433203212
4222132534Y111112220021218H
DISCUSSION
Numerical Abnormalities. Cytogenetic studies of testicular
germ cell tumors (17, 21-32) have demonstrated the presence
of a generally hyperdiploid to hypotriploid chromosome com
plement, with higher modal chromosome numbers in seminomas than in NSGCT. Similar results were obtained by meas
uring the DNA content of the different subtypes of testicular
germ cell tumors (33).
Plotting the number of reported primary NSGCT (21-28,
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CYTOGENETirS.
PLOIDY, AND PATHOGENESIS OF NSGCT
N It
1
S3
4
5
n—¿a—it¿—tt
«iw—¿
it—¿
HI«
10
11
12
I
•¿
J Aie
•¿Ã©l
I il
1B
15
13
17
I
i «—r
it
1S
19
20
I
«
I
Fig. 1. Karyotype of a metaphase of case 3 (the karyotypical description is given in Table 2).
H U
im u-w-i
10
13
21
14
III"*
11
12
\
II 111 II
I
If Ut
H l
H
IS
1B
T7
IB
19
2O
22
Fig. 2. Karyotype of a metaphase of case 9 (the karyotypical description is given in Table 2).
30, 31) against their modal ranges (Fig. 6), it is clear that most
NSGCT have between 60 and 64 chromosomes, and only very
few are not peritriploid. At variance, although most seminomas
have between 65 and 69 chromosomes, higher numbers are not
unusual in these tumors (13).
Several hypotheses have been proposed on the mechanism of
origination of aneuploidy in testicular germ cell tumors: suc
cessive nondisjunctions of a diploid cell; polyploidization or
cell fusion; followed and/or preceded by chromosomal gain
and/or loss (see Ref. 34 for review). If successive nondisjunction
of a diploid cell were a mechanism of oncogenesis of NSGCT,
one would expect a higher frequency of near diploid NSGCT
and lower frequencies in higher classes. Since the opposite is
observed, there should be other modes of origin of aneuploidy.
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CYTOGENETICS.
PLOIDY. AND PATHOGENESIS
OF NSGCT
tr»
4
5
u—F—fit—mi—«—if
12
11
il m ei
13
1B
15
S1
so
IS
SS
tÃ-m
Fig. 3. Karyotype of a metaphase of case 10. The t(6;l9)(ql3;pl3.2)
ìli
«•*
17
is not clonal ((he remaining karyotypical description is given in Table 2).
mini
4
5
Ã-iiÃ-«
imi}iiiuhi«-mi-î«j
iimi
I
10
wir
Utili
11
U« Mil ijmriu
15
13
U
1B
17
1S
19
SO
-•-*«•«•*-
Fig. 4. Karyotype of a metaphase of case 14 (the karyotypical description is given in Table 2).
The clear peak in the hypotriploid range is in keeping with
the measured DNA content of testicular germ cell tumors (33)
and can be explained by loss of chromosomes starting from a
triploid or tetraploid cell. This would be in keeping with the
model of pathogenesis of testicular germ cell tumors proposed
by Ewing (6) and Friedman (1). According to this model most
testicular germ cell tumors, irrespective of their histology,
would originate in a carcinoma in situ cell and progress through
a seminoma stage. In disagreement with the tumor progression
model proposed by Nowell (35, 36), according to which the
clonal evolution of a tumor cell population goes from diploid
to higher chromosome numbers, the progression of testicular
germ cell tumors apparently goes from high to lower numbers
of chromosomes, i.e., is accompanied by a net loss of chromo
somal material. This decrease is probably the end result of the
loss of specific chromosomes, the development of structural
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CYTOGENETICS,
PLOIDV.
AND
1.4
1.2 _
1.0 _
0.8 _
0.6 _
0.4 _
0.2 _
-
0.0 _
-0.2 _
-0.4.
-0.6 _
-0.8
11 18 22 1 10 9 4 19 5 13 15 14 Y 2 16 6 3 20 17 21 7 8 12 X
CHROMOSOMES ORDERED BY FREQUENCY
Fig. 5. Mean standardized number of normal copies of chromosomes com
pared to 2, in 14 NSGCT. The total number of normal chromosomes per case
was standardized to 46; the mean number of sex chromosomes was multiplied by
2, in order to allow an easier comparison with the autosomes.
abnormalities, and the gain of some other chromosomes (or
part of chromosomes).
It has been suggested that loss of certain chromosomes or
(loss of heterozygosity for) some chromosomal regions is im
portant for the development of malignancy, presumably because
of loss of genes with tumor suppressing and differentiation
regulating properties (37-45).
If loss of chromosomes in testicular germ cell tumors is
related to loss of genes crucial for normal cell differentiation,
different chromosomes should be underrepresented in NSGCT
as compared to seminomas. However, since both are germ cell
tumors, it should not be surprising that some chromosomes are
underrepresented in both subtypes. Tables 2 and 3 and Fig. 5
give an idea of which chromosomes and part of chromosomes
are over- or underrepresented in NSGCT. As can be seen,
chromosomes 4, 5, 9, 10, 11, 13, 14, 15, 18, 22, and Y are
usually underrepresented, whereas chromosomes 7, 8, 12 (es
pecially its short arm), and X are usually overrepresented. It is
of interest that chromosome 15 is overrepresented in semino
N
U
M
B
E
R
PATHOGENESIS
OF NSGCT
mas (13) and underrepresented in NSGCT, while chromosome
17 is underrepresented in the former, but not in the latter. It
might be speculated that chromosome 15 contains genes im
portant for sperm cell differentiation. Chromosomes more fre
quently represented in NSGCT than in seminomas (e.g. chro
mosome 17) may contain genes responsible for a more malig
nant development.
The rare occurrence of NSGCT with chromosome numbers
higher than 69 can also be fitted into this model. If loss of
heterozygosity for a certain chromosome region plays an im
portant role in the progression of a cell from the seminoma to
the NSGCT stage (which remains to be proved), it will be in
the triploid range that chromosome loss will be most critical.
As a matter of fact, if a cell contains three copies of a certain
autosome, e.g., two paternal and one maternal, the probability
of becoming homozygous for the paternal chromosome through
random loss of a single chromosome is 1:3, whereas for a
tetraploid cell two random events would be necessary (proba
bility, 1:6). Accordingly, the higher the chromosome number in
a seminoma stage cell, the lower is the probability of obtaining
a NSGCT.
Structural Abnormalities. As can be seen in Table 2, in
primary NSGCT chromosome 12 is very often involved in
structural abnormalities, which was also noted by Gibas et al.
(30) and DeLozier-Blanchet et al. (32). Twelve of 14 tumors
had 1 or more copies of i(12p), a specific marker for germ cell
tumors of the testis (28-30, 32) and possibly also of the ovary
(46, 47). Two tumors, however, lacked that marker. These
i(12p) negative testicular germ cell tumors may represent a
different group of tumors with a different clinical evolution
(19).
Besides the i(12p) we did not find any structural abnormality
in common with different tumors.
As is the case for seminomas (13, 16), chromosome 1 is also
frequently involved in structural abnormalities in NSGCT (Ta
ble 2). In 4 of 6 primary NSGCT reported by Gibas et al. (30),
and in the case described by Saikevych et al. (31), there were
also structural abnormalities of chromosome 1. In cell lines
14 _
O
F
B _
C
A
S
E
S
4 _
2 _
<50
50-54
55-59
60-64
65*9
70-74
75-79
KW4
8549
90-94
95-99
100-4
105-9
110-4
>115
MODAL RANGE
Fig. 6. Estimated number of reported primary NSGCT by chromosome count. When the reported modal counts of a case would not fit in a single class in the
graph, the case was plotted as equal fractions in the corresponding classes. Besides our 14 cases, 5 NSGCT reported by Gallon et al. (22), 1 by Miles (23), 3 by Rigby
(24). 4 by Lelikova et al. (26), 4 by Atkin (27), 1 by Atkin and Baker (28), 6 by Gibas et al. (30), 1 by Saikevych et al. (31), and 2 by Martineau (unpublished data,
quoted by Atkin (27)) were included in this graph.
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CYTOGENETICS,
PLOIDY. AND PATHOGENESIS
derived from testicular germ cell tumors abnormalities of chro
mosome 1 are also very common (49-51). Wang et al. (48)
found a nonrandom involvement of chromosome 1 in structural
and numerical abnormalities in each of 14 NSGCT-like tumor
cell lines. The breakpoints most often found were at Ipl2,
p22,p36, and ql2. The same or contiguous bands were involved
in the present series. Chromosome 1 rearrangements, however,
have been found in a variety of other solid tumors and in many
hematological malignancies (see Ref. 52 for review). Yet, as our
results show, chromosome 1 is much more frequently involved
in testicular germ cell tumors than in any other tumor.
In the present series we noted structural abnormalities in
volving 73 different breakpoints (Table 2), 22 of which had
been reported by Gibas et al. (30) and Saikevych et al. (31) in
their studies of NSGCT. Since many breakpoints described
(e.g., in chromosomes 1, 4, 8, and 11) are also found in other
kinds of malignancies (see Ref. 52 for review), they should
probably be considered proliferation specific rather than differ
entiation associated breakpoints (53).
REFERENCES
1. Mostofi, F. K.. and Sobin, L. H. International histological classification of
testicular tumors (No. 16). International Histologie Classification of Tumors.
Geneva: WHO, 1977.
2. Mostofi, F. K. Pathology and germ cell tumors of testis. Cancer (Phila.), 45:
1735-1754, 1980.
3. Mostofi. F. K.. Sesterhenn, I. A., and Davis. C. J.. Jr. World Health
Organization International Histological Classification of Germ Cell Tumours
of the Testes. Adv. Biosci., 55: 1-23, 1986.
4. Pugh. R. C. B. Combined tumours. In: R. C. B. Pugh (ed.). Pathology of the
Testis. Oxford. United Kingdom, pp. 245-258. Blackwell Publications, 1976.
5. Brawn, P. N. The origin of germ cell tumors of the testis. Cancer (Phila.),
51: 1610-1614, 1983.
6. Ewing, J. Teratoma testis and its derivatives. Surg. Gynecol. Obstet., 12:
230-261, 1911.
7. Friedman, N. B. The comparative morphogenesis of extragenital and gonadal
teratoid tumors. Cancer (Phila.), 4: 265-276. 1951.
8. Pierce. G. B., and Abell, M. R. Embryonal carcinoma of the testis. Pathol.
Annu., 5: 27-60, 1970.
9. Raghavan, D., Sullivan, A. L., Peckham, M. J.. and Neville. A. M. Elevated
serum alphafetoprotein and seminoma. Clinical evidence for a histologie
continuum? Cancer (Phila.). 50: 982-989. 1982.
10. Sesterhenn. 1. A. The role of intratubular malignant germ cells in the
histogenesis of germ cell tumours. In: W. G. Jones, A. Milford Ward, and
C. K. Anderson (eds.). Germ Cell Tumours II, Proceedings of the Second
Germ Cell Tumours Conference, pp. 25-35. Elmsford NY. Pergamon Press,
1985.
11. Kiss, F., and Jubasz. J. Testicular germ cell tumors, current problems of
histogenesis and classification. Int. Urol. Nephrol.. 17: 85-95, 1985.
12. Oliver. R. T. D. HLA phenotype and clinicopathological behaviour of germ
cell tumours: possible evidence for clonal evolution from seminomas to
NSGCT. Int. J. Androl., 10: 85-94. 1987.
13. Castedo, S. M. M. J., De Jong, B., Oosterhuis, J. W., Seruca, R., Te
Meerman, G., Dam, A., and Koops. H. S. Cytogenetic analysis often human
seminomas. Cancer Res., 49: 439-443, 1989.
14. Castedo, S. M. M. J.. De Jong. B., Oosterhuis, J. W., Seruca. R., Buist, J.,
and Koops, H. S. Cytogenetic study of a combined germ cell tumor of the
testis. Cancer Genet. Cytogenet., 35: 15-165, 1988.
15. Oosterhuis, J. W., de Jong, B., Cornelisse. C. J., Molenaar, W. M., Meiring.
A., Idenburg. V. J. S., Schraffordt, Koops. H., and Sleijfer, D. T. Karyotyping
and DNA flow cytometry of mature residual teratoma after intensive chemo
therapy of disseminated nonseminomatous germ cell tumor of the testis: a
report of two cases. Cancer Genet. Cytogenet., 22: 149-157. 1986.
16. Gibas, L. M., Gibas. Z., and Sandberg, A. A. Technical aspects of Cytogenetic
analysis of human solid tumors. Karyogram, 10: 25-27, 1984.
17. Atkin, N. B., and Baker. M. C. Chromosome analysis of three seminomas.
Cancer Genet. Cytogenet., 17: 315-323, 1985.
18. Peckham, M. J., Berret, A., McElwain, T. J.. and Hendry, W. F. Combined
management of malignant teratoma of the testis. Lancet, 2: 267-270, 1979.
19. Castedo. S. M. M. J., De Jong, B., Oosterhuis, J. W., Seruca, R., Idenburg.
V., Buist. J., and Sleijfer. D. T. "i( 12p) negative" testicular germ cell tumors.
A different group? Cancer Genet. Cytogenet., 35: 171-178. 1988.
20. Castedo, S. M. M. J., Oosterhuis, J. W.. De Jong, B.. Seruca, R.. Dam, A.,
Buist, J., Koops, H. S.. and Sleijfer D. T. A residual mature teratoma with a
more balanced karyotype than the primary testicular NSGCT? Cancer Genet.
Cytogenet., 32: 51-57, 1988.
OF NSGCT
21. Martineau, M. A similar marker chromosome in testicular tumors. Lancet,
7:839-842, 1966.
22. Galton. M.. Benirschke, K., Baker, M., and Atkin, N. B. Chromosomes of
testicular teratomas. Cytogenetics, 6: 261-275, 1966.
23. Miles. C. P. Chromosome analysis of solid tumors. I. Twenty-eight nonepithelial tumors. Cancer (Phila.). 20: 1253, 1967.
24. Rigby, C. C. Chromosome studies in ten testicular tumors. Br. J. Cancer.,
22:480. 1968.
25. Martineau. M. Chromosomes in human testicular tumours. J. Pathol.. 99:
271-282. 1969.
26. Lelikova. G. P., Laskina. A. V.. Zakharov, A. F., and Pogosyants, E. E.
Cytogenetic study of human seminomas. Vopr. Onkol., 17: 20, 1971 [quoted
by Atkin (26)).
27. Atkin, N. B. High chromosome numbers of seminomata and malignant
teratoma of the testis: a review of data on 103 tumours. Br. J. Cancer., 28:
275-279, 1973.
28. Atkin, N. B., and Baker, M. C. i(12p): specific chromosomal marker in
seminoma and malignant teratoma of the testis? Cancer Genet. Cytogenet..
10: 199-204. 1983.
29. DeLozier-Blanchet. C. D.. Engel. E., and Walt. H. Isochromosome 12p in
malignant testicular tumors. Cancer Genet. Cytogenet.. 15: 375-376, 1985.
30. Gibas, Z., Prout, G. R., Pontes, J. E., and Sandberg, A. A. Chromosome
changes in germ cell tumors of the testis. Cancer Genet. Cytogenet., 19:245252. 1986.
31. Saikevych, 1. A., Mayer, M., Brooks, V. P., and Michael, S. Cytogenetic
study of a testicular tumor in a translocation (13:14) carrier. Cancer Genet.
Cytogenet., 26: 299-307, 1987.
32. DeLozier-Blanchet, C. D.. Walt, H., Engel, E., and Vaugnat, P. Cytogenetic
studies of human testicular germ cell tumors. Int. J. Androl. 70:69-78, 1987.
33. Oosterhuis. J. W., Castedo. S. M. M. J., De Jong, B., Cornelisse, C. J., Dam,
A., Sleijfer, D. T., and Koops, H. S. Ploidy of subtypes of primary germ cell
tumors of the testis. Pathogenetic and clinical relevance. Lab. Invest.. 60:
14-21. 1989.
34. Sandberg, A. A. In: The Chromosomes in Human Cancer and Leukemia, pp.
511-515. Amsterdam: Elsevier, 1980.
35. Nowell, P. C. Tumor progression and clonal evolution: the role of genetic
instability. In: Chromosome Mutation and Neoplasia, pp. 413-432. New
York: Alan R. Liss. 1983.
36. Nowell, P. C. Mechanisms of tumor progression. Cancer Res.. 46: 22032207, 1986.
37. Klinger. H. P., and Kaelbing, M. Suppression of tumorigenicity in somatic
cell hybrids. Cytogenet. Cell Genet., 42: 225-235, 1986.
38. Srivatsan, E. S., Benedict, W. F., and Stanbridge, E. J. Implication of
chromosome 11 in the suppression of neoplastic expression in human cell
hybrids. Cancer Res., 46: 6174-6179, 1986.
39. Stanbridge, E. J., Flandermeyer, R. R., Daniels, D. W., and Nelson-Rees,
W. A. Specific chromosome loss associated with the expression of tumori
genicity in human cell hybrids. Somatic Cell Genet., 7: 699-712. 1981.
40. Kaelbling, M., and Klinger. H. P. Suppression of tumorigenicity in somatic
cell hybrids. Cytogenet. Cell Genet., 41: 65-70, 1986.
41. Sager. R., and Kovac, P. E. Genetic analysis of tumorigenesis. I. Expression
of tumor-forming ability in hamster hybrid cell lines. Somatic Cell Genet.,
4:375-392. 1978.
42. Stanbridge. E. J., Der, C. J., Doersen, C-J.. Nishimi, R. Y., Peehl, D. M.,
Weissman, B. E., and Wilkinson, J. E. Human cell hybrids: analysis of
transformation and tumorigenicity. Science (Wash. DC), 215: 252-259,
1982.
43. Evans, E. P., Burtenshaw, M. D., Brown, B. B., Hennion. R., and Harris, H.
The analysis of malignancy by cell fusion. J. Cell Sci., 56: 113-130, 1982.
44. Benedict, W. F., Weissman, B. E., Mark, C., and Stanbridge, E. J. Tumori
genicity of human HT1080 fibrosarcoma x normal fibroblast hybrids: chro
mosome dosage dependency. Cancer Res., 44: 3471-3479, 1984.
45. Kaelbling, M.. Roginski, R. S., and Klinger, H. P. DNA polymorphisms
indicate loss of heterozygosity for chromosome 11 of D98AH2 cells. Cyto
genet. Cell Genet.. 41: 240-244. 1986.
46. Atkin. N. B., and Baker. M. C. Abnormal chromosomes including small
metacentrics in 14 ovarian cancers. Cancer Genet. Cytogenet.. 26: 355-361,
1987.
47. Jenkyn, D. J., and McCartney, A. J. A chromosome study of three ovarian
tumors. Cancer Genet. Cytogenet., 26: 327-337, 1987.
48. Wang, N., Trend, B.. Bronson, D. L., and Frally, E. E. Nonrandom abnor
malities in chromosome 1 in human testicular cancers. Cancer Res., 40: 796802. 1980.
49. Parrington, J. M., and West, L. F. Loss of chromosome and enzyme markers
in cultures from testicular tumours. Clin. Genet., 27: 326, 1985.
50. Parrington, J. M.. West, L. F., and Povey, S. Chromosome changes in germ
cell tumours. In: W. G. Jones, A. Milford Ward, and C. K. Anderson (eds.),
Germ Cell Tumours II, Proceedings of the Second Germ Cell Tumours
Conference, pp. 61-67. Elmford, NY: Pergamon Press, 1985.
51. Parrington, J. M., and West, L. F. Different chromosome No. 1 markers and
loss of Ip material in separate cell lines from the same testicular teratoma.
In: Seventh International Congress on Human Genetics, Berlin, 1986.
52. Mitelman, F. Catalog of Chromsome Aberrations in Cancer. Ed. 2. New
York: Alan R. Liss. 1985.
53. Heim, S., and Mitelman, F. Proliferation-specific and differentiation-asso
ciated chromosomal breakpoints in human neoplasia. A unifying model.
Hereditas. 104: 307-312. 1986.
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Chromosomal Changes in Human Primary Testicular
Nonseminomatous Germ Cell Tumors
Sérgio M. M. J. Castedo, Bauke de Jong, J. Wolter Oosterhuis, et al.
Cancer Res 1989;49:5696-5701.
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