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Am. J. Hum. Genet. 47:635-643, 1990
Genetics and Biology of Human Ovarian Teratomas. 1.
Cytogenetic Analysis and Mechanism of Origin
Urvashi Surti,*,t Lori Hoffner,* Aravinda Chakravartit and Robert E. Ferrellt
*Department of Pathology, Magee-Womens Hospital; and tDepartment of Human Genetics, University of Pittsburgh, Pittsburgh
Summary
One hundred and two benign, mature ovarian teratomas and two immature, malignant teratomas were
karyotyped and scored for centromeric heteromorphisms as part of an ongoing project to determine the
chromosomal karyotype and the genetic origin of ovarian teratomas and to assess their utility for gene-
centromere mapping. Karyotypic analysis of the benign cases revealed 95 46,XX teratomas and 7 chro-
mosomally abnormal teratomas (47,XXX, 47,XX,+8 [two cases], 47,XX,+15, 48,XX,+7,+12,
91,XXXX,-13 [mosaic], 47,XX,-15,+21,+mar). Our study reports on the first cases of tetraploidy and
structural rearrangement in benign ovarian teratomas. The two immature cases had modal chromosome
numbers of 78 and 49. Centromeric heteromorphisms that were heterozygous in the host were homozy-
gous in 65.2% (n = 58) of the benign teratomas and heterozygous in the remaining 34.8% (n = 31).
Chromosome 13 heteromorphisms were the most informative, with 72.7% heterozygosity in hosts. The
cytogenetic data indicate that 65% of teratomas are derived from a single germ cell after meiosis I and
failure of meiosis II (type II) or endoreduplication of a mature ovum (type III); 35% arise by failure of
meiosis I (type I) or mitotic division of premeiotic germ cells (type IV).
Introduction
Benign ovarian teratomas account for approximately
11% of all ovarian tumors. Ovarian teratomas develop
from a totipotent germ cell, are composed of fully
differentiated histologic tissue, and frequently contain
ectodermal, mesodermal, and endodermal structures.
The appearance of ovarian teratomas is quite unusual,
as many contain bone, hair, neural tissue, sebaceous
material, skin, and fully developed teeth. Almost 100%
of cases contain skin, hair and sebaceous material, 30%
are composed exclusively of skin and dermal append-
ages, 38% have only skin and neural tissue, while 32%
contain skin and neural tissue as well as various other
tissues (Damjanov 1983). Clinically, ovarian teratomas
may occur at any age; cases have been reported from
2 years to 88 years of age. However, teratomas are de-
Received December 18, 1989; revision received April 24, 1990.
Address for correspondence and reprints: Urvashi Surti, Ph.D.,
Department of Pathology, Magee-Womens Hospital, Forbes and
Halket Streets, Pittsburgh, PA 15213.
i 1990 by The American Society of Human Genetics. All rights reserved.
0002-9297/90/4704-0008$02.00
tected most frequently during the childbearing years,
with the median age being 30 years. The size of these
tumors also varies considerably; a review of the litera-
ture shows a range from less than 1 cm to 45 cm in
diameter. In addition, ovarian teratomas may occur
unilaterally or bilaterally (7.9%-15% ) in the host (Peter-
son et al. 1955). Whereas most mature ovarian tera-
tomas are benign, malignant degeneration occurs in ap-
proximately 1.9% of cases (Climie and Heath 1968).
The most common neoplasm to develop is squamous-
cell carcinoma (80%), adenocarcinoma and melanoma
being much more rare.
In addition to the benign mature teratomas, there is
a second category of ovarian teratomas, namely, the
immature teratomas. Immature teratomas account for
approximately 1%-2% of all ovarian teratomas
(Ohama et al. 1985), contain immature elements, and
have a high propensity for malignancy.
Cytogenetic analysis of benign ovarian teratomas usu-
ally reveals a normal 46,XX karyotype, but trisomy,
triploidy, and mosaicism have also been found (Ohama
1987). Early cytogenetic analysis revealed that, although
these cysts were usually 46,XX, they frequently differed
635
Surti et al.
genetically from their host. That is, if the female host
was heterozygous for a particular centromeric heter-
omorphism, the teratoma was found to be homozygous
(Linder et al. 1975; Patil et al. 1978). In 1975, Linder
et al. reported data on six ovarian teratomas: elec-
trophoretic enzyme polymorphisms were used in con-
junction with centromeric chromosome heteromor-
phisms to determine the origin of benign cystic
teratomas. In all cases where the host was heterozy-
gous at the centromere, the teratoma was shown to be
homozygous. Occasionally, distal isozyme loci that were
heterozygous in the host remained heterozygous in the
teratoma, while the centromeric markers in the tera-
toma were homozygous. From these findings, Linder
et al. concluded that cystic teratomas were derived from
a single germ cell after the first meiotic division, either
by suppression of meiosis II or fusion of the second
polar body with the ootid. In 1978, Patil et al. reported
on 21 cases of benign ovarian teratomas. In every case
the teratoma had homozygous centromeric markers,
while the distal markers were heterozygous or homozy-
gous. These findings confirmed Linder et al.'s theory
and suggested the occurrence of recombination in ovar-
ian teratomas. Carritt et al. (1982) studied seven ovar-
ian teratomas arising in a single patient. These authors
reported that four of the tumors had centromeric mark-
ers identical to those found in the host and postulated
that failure of meiosis I could also be a mechanism for
the origin of ovarian teratomas. Parrington et al. (1984)
studied 21 benign ovarian teratomas and found that
13 had homozygous centromeric markers and eight had
heterozygous centromeric markers where the host was
heterozygous. However, 11 ofthe 13 teratomas that were
homozygous for chromosomal markers were also
homozygous for all enzyme polymorphisms tested. To
explain this complete homozygosity, Parrington et al.
proposed yet another mechanism of origin, namely en-
doreduplication of a mature ovum. In 1987, Ohama
reported chromosomal heteromorphisms and HLA
polymorphisms in 128 cases (Ohama 1987). His data
revealed cases thought to result from meiosis I failure,
meiosis II failure, endoreduplication of a mature ovum,
and mitotic proliferation of a premeiotic germ cell.
These studies suggested multiple mechanisms of ori-
gin for teratoma formation. In all, five mechanisms of
origin have been postulated (Surti et al. 1988):
VI. Failure of meiosis I or fusion of the first polar
body with the oocyte
II. Failure of meiosis II or fusion of the second
polar body with the ootid
III. Duplication of the genome of a mature ovum
IV. Failure of meiosis I and II in the primordial
germ cell
IV. Fusion of two ova
In general, teratoma formation appears to be a
manifestation of defective meiosis. The exact nature
of the meiotic error can be discerned in most cases with
the use of chromosomal heteromorphisms and avail-
ability of distal polymorphic DNA markers that are
much more informative than isozyme analysis. As
shown in table 1, teratomas originating due to a meio-
sis I error (type I), would be expected to be heterozy-
gous for all centromeric markers for which the host
was heterozygous. Distal markers could be heterozy-
gous or homozygous depending on the occurrence and
frequency of crossing-over between the centromere and
the marker. Thus, the absence of crossovers will result
in heterozygous distal markers, a single crossover will
result in 50% homozygosity of the distal marker, and
double crossovers will result in 75% heterozygosity of
distal markers. A meiosis II error (type II) would pro-
duce teratomas in which all markers near the centro-
mere would be homozygous. Distal markers could be
homozygous or heterozygous, depending on crossover
events (Chakravarti et al. 1989). For teratomas originat-
ing through endoreduplication (type III), all centromeric
and distal markers would be homozygous. Total lack
of meiosis of a primordial germ cell (type IV), followed
by mitotic division, would produce teratomas in which
all centromeric and distal markerswould be identical
to the host. Teratomas originating through fusion of
two ova (type V), would have, on the average, an equal
number of heterozygous and homozygous centromeric
markers. On the basis of chromosomal heteromor-
phisms alone, the types I and IV cannot be distinguished
because both these groups have heterozygous pericen-
tromeric regions. Similarly, types II and III cannot be
distinguished because of homozygous pericentromeric
Table I
Mechanisms of Origin of Ovarian Teratomas
TERATOMA GENOTYPE ATa
TYPE MECHANISM CENTROMERE DISTAL MARKER
I .... Meiosis I error + + ,-
II.... Meiosis II error - + ,-
III .... Endoreduplication
IV .... No meiosis + +
V .... Fusion of two ova +,-
a + = Heterozygous; - = homozygous.
636
Chromosomal Origin of Ovarian Teratomas
regions in both. With the use of highly polymorphic
single-gene probes and minisatellite probes the distinc-
tion between these types can be made for each case.
Due to their unique parthenogenic origin, ovarian
teratomas provide us with a useful tool to study recom-
bination. In type I and type II ovarian teratomas two
of the four products of meiosis (half tetrads) can be
recovered and used for mapping genes relative to the
centromere. The statistical methods for analysis of chro-
mosome and marker data have been developed using
specific mapping functions (Ott et al. 1976; Chakravarti
et al. 1986; Chakravarti et al. 1989). As mentioned,
centromeric and noncentromeric markers can define the
heterozygosity or homozygosity of different segments
of a chromosome, thus allowing for detection of cros-
sover events. In this article, we present the detailed results
of the cytogenetic analysis of 102 mature ovarian tera-
tomas.
Subjects and Methods
Patients
Samples were obtained from 104 patients who were
operated on at Magee-Womens Hospital. Seventeen
cases were obtained from 1983 to 1986, and 91 cases
were obtained consecutively from April of 1986 to April
of 1989. One immature case was received from Chil-
dren's Memorial Hospital in Chicago. The patients
ranged in age from 9 years to 75 years, with a mean
of 31 years. There was no selection for patients, the
criteria for inclusion into the study being the availabil-
ity of adequate tissue from both teratoma and host,
and successful tissue-culture growth. The diagnosis of
benign teratoma was confirmed for each case by pathol-
ogy reports. Most of the samples were dissected by one
individual to ensure uniform selection. The host tissue
was either fallopian-tube or normal ovary; however, if
this was not available, a portion of the outer most cyst
wall was used. Previous studies have shown that this
is always genetically representative of the host, rather
than the teratoma (Parrington et al. 1984). Tissue from
the growth nidus or innermost cell wall of the cyst was
selected for the teratoma tissue. A piece of normal tis-
sue as well as the teratoma tissue was snap frozen for
DNA analysis.
Tissue Culture
Tissue samples were minced and dissociated with a
1% trypsin solution, followed by 0.64% collagenase
solution. The cells were grown in Chang Medium at
370C in a humidified atmosphere with 5% C02. Fresh
medium was added every 2-3 d. Once growth was well
established, cells were subcultured, usually every 4-6 d.
Cells from each patient were cryopreserved in liquid
nitrogen for DNA analysis and regrown as needed.
Cytogenetics
Chromosomal preparations were usually obtained be-
tween 1-5 passages in culture. Metaphase cells were
arrested with colcemid, collected following a 4-h in-
cubation, and treated with .032 M KCI. The cells
were fixed with a cold 1:3 glacial acetic acid/methanol
solution and spread on a cold slide. The slidewas stained
with dichloromethoxyacridine, (CMA)2S, and scanned
with an Olympus BH-2 fluorescence microscope. At
least 20 metaphases were counted and scored for Q-
band heteromorphisms for both the host and teratoma
according to International System for Human Cytoge-
netic Nomenclature (ISCN 1985). The heteromorphic
areas were scored on a scale of 1-5, first by size and
then by staining intensity, frequently by two indepen-
dent observers (fig. 1). C-banding was also used as a
complementary method for analyzing centromeric het-
eromorphisms (Mangold and Meisner 1988).
Results
One hundred and nine ovarian teratomas from 104
patients (five bilateral) were set up for culture. Successful
culture was obtained in 104 cases for both host and
teratoma. Ofthese 104 teratomas, 100 were mature, two
were mature with malignant degeneration (squamous-
cell carcinoma), and two were classified as immature
malignant teratomas. Out offive bilateral teratomas suc-
cessful growth was obtained in four cases.
Mature Teratomas
Karyotypic analysis of the mature benign cases re-
vealed a 46,XX genotype in 95 cases. Numerical ab-
normalities were detected in six cases. These include
47,XXX, 47,XX,+8 (two cases), 47,XX,+15,
48,XX,+7,+12, and 91,XXXX,-13. The tetraploid
case had three cell lines, with 91,XXXX,-13 being the
predominant cell line (table 2). A structural abnormal-
ity was detected in only one case. This teratoma had
a karyotype of 47,XX,-15,+21,+mar, in which the
marker chromosome is believed to be a derivative of
chromosome 15. The two mature cases with malignant
degeneration had a 46,XX karyotype.
The heteromorphism data are summarized in table
2, and show that of the 102 cases 89 (87%) had in-
637
Figure I Examples of heteromorphic variants observed on chromosomes 1, 3, 4, 9, 13-16, 21, and 22
Chromosomal Origin of Ovarian Teratomas
formative markers. Thirty-one cases had heterozygous
centromeric markers for both the host and teratoma,
while in 58 cases the centromeric markers were hetero-
zygous for the host and homozygous for the teratoma,
indicating that 65% of the teratomas are type II or III
and 35% are type I or IV (tables 1, 2). Chromosome
13 heteromorphisms, with 72.7% heterozygosity, ap-
peared to be the most informative markers. Further-
more, the number of informative markers, per case,
ranged from one to seven with an average of 3.5 mark-
ers. The average age of the patients with homozygous
centromeric markers was 30.8 years (range 9-62) and
of those with heterozygous markers was 29.7 years
(range 18-49). Mechanism of origin of a benign ovar-
ian teratoma did not seem to correlate with its clinical
presentation (age of the patient, size and tissue compo-
sition of the teratoma) using the number of cases avail-
able at this time. Out of four bilateral teratoma pairs
with successful cell growth, seven were 46,XX and one
was 47,XX,+15. Three pairs with informative heter-
omorphisms revealed two pairs having one homozy-
gous and one heterozygous teratoma each and one pair
with both homozygous teratomas. Average age of the
patients with trisomies was 26.3 years (range 9-40).
Two of these six patients were above 35 years of age.
Immature Teratomas
Two immature teratomas were studied. One tumor
was from the right ovary of a 16-year-old female, the
other was from the left ovary of a 3-year-old female.
Karyotypic results on the two immature ovarian tera-
tomas show that one teratoma had a modal chromo-
some number of78,XXXX and the other had a modal
karyotype of 49,XX,+ 8,+12,+22. Q-band heteromor-
phisms for both cases illustrate heterozygous centro-
meric markers, thus indicating that the tumors origi-
nated from a germ cell prior to the completion ofmeiosis
I (type I or type IV). The frequency of meiosis I error
in immature teratomas is thought to be similar to that
found in benign cystic teratomas (Ohama 1987). This
suggests that immature teratomas and benign cysticter-
atomas probably have similar mechanisms of origin.
Detailed histological findings along with the clinical
follow-up of these immature cases will be published
separately.
Discussion
Ovarian teratomas were documented as early as the
17th century. The word teratoma comes from the Greek
word teras, meaning monster, and the suffix -oma,
meaning swelling. The origin of these cysts wascon-
sidered to be evil, and early speculations included the
invasion of a parasitic demon or the outcome of vari-
ous forms of sexual misbehavior (Wheeler 1983). Re-
cent studies using analyses of isozyme, HLA, DNA,
and cytogenetic markers show that most ovarian tera-
tomas arise due to defective meiotic processes (Deka
et al. 1990). Five mechanisms of origin have been postu-
lated: meiosis I error, meiosis II error, endoreduplica-
tion of a haploid ovum, mitotic division of a premeiotic
germ cell, and fusion oftwo ova. The two earliest studies
utilized only enzyme markers (Linder 1969; Linder and
Power 1970). Subsequently, two studies (Linder et al.
1975; Patil et al. 1978) included enzyme and chro-
mosomal data on 21 cases of benign ovarian teratomas,
and in every case, the centromeric markers were het-
erozygous in the host and homozygous in the teratoma.
These findings are inconsistent with the results of other
studies that have followed. Data from Parrington (1984),
Ohama (1987), and the present study all show the oc-
currence of heterozygous centromeric markers in ovar-
ian teratomas to be approximately 35%-38%. It is
speculated that the earlier studies found only homozy-
gous chromosomal markers due to noninformative chro-
mosomal markers in some cases. Currently, the combi-
nation of cytogenetic data and highly polymorphic
DNA markers, including VNTR probes, can provide
further information on the precise origin specially
delineating type I from type IV and type II from type
III (Deka et al. 1990).
Several technical points merit consideration in evalu-
ating our data. Although great effort was made to sep-
arate host and teratoma tissue for culture, mixed cell
cultures are always a possibility. In two cases, cross-
contamination of normal host cells was detected in the
cultured teratoma cells (cases 20 and 34), based on a
difference in chromosomal zygosity between the host
and teratoma. However, if the host and teratoma both
had the same zygosity, one would not be able to detect
a mixed population. Detecting contamination from nor-
mal cells is necessary if cultured cells from teratoma
are to be used for studying other genetic markers.
The inability to differentiate between normal and ter-
atoma cells, when the two tissues have the same chro-
mosomal markers, is also a concern when calculating
the frequency of teratomas with heterozygous mark-
ers, especially in the cases where recombination is not
identified by DNA markers. One possibility for over-
coming this problem is to use an immunohistochemi-
cal stain that would preferentially stain either the host
or the teratoma cells. Then, the differentially stained
639
Table 2
Cytogenetic Analysis of 102 Mature Teratomas
TERATOMA INFORMATIVE HETEROMORPHISMS
Karyotype
46,XX
46,XX
46,XX
47,XX,+8
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
47,XX,-15,+21,+M
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
46,XX
47,XXX
46,XX
Number
2
2
4
4
6
3
4
4
2
1
4
3
2
7
2
3
1
S
6
3
7
4
S
3
4
7
3
3
1
7
S
3
7
4
3
4
S
6
2
4
3
1
S
6
6
6
4
Chromosome number
1, 9, 14, 15, 22
3, 13
3, 13
3, 13-15
3, 9, 13, 15
1, 3, 13-15, 21
3, 4, 13
3, 13, 21, 22
1, 14, 15, 22
9, 15
3
3, 9, 14, 21
4, 21, 22
13, 14
3, 4, 9, 14, 15, 21, 22
9, 13
3, 15, 21
13
1, 3, 13-15, 22
4, 13-15, 21, 22
3, 13-15, 21
3, 13-15, 21
3, 13, 21
1, 3, 9, 13, 15, 21, 22
13, 14, 15, 21
3, 4, 9, 13, 15
3, 14, 21
3, 4, 13, 15
3, 13, 15, 21, 22
3, 14, 15, 21, 22
1, 3, 4, 13, 14, 21, 22
13, 15, 22
16, 21, 22
3, 9, 13, 14, 21
14
1, 3, 4, 13, 14, 21, 22
3, 13, 14, 15, 21
13, 14, 22
1, 4, 9, 13, 14, 21, 22
3, 13, 14, 15
13, 14, 15
3, 13, 14, 15
3, 9, 13, 14, 15
1, 3, 13, 15, 21, 22
13, 15
13, 14, 15, 22
3, 15, 22
13
3,13, 15, 21, 22
3,13, 14, 15, 21, 22
3,13, 14, 15, 21, 22
4, 9, 13, 15, 21, 22
3, 9, 13, 22
640
CASE
1........
2b .......
3b .. .. .. .
4........
5 ........
6........
7........
8........
9........
10 .......
11 .......
12.......
13.......
14.......
15 .......
16.......
17.......
18.......
19 .......
20.......
21b ......
22b ......
23.......
24.......
25.......
26.......
27.......
28.......
29.......
30.......
31.......
32.......
33.......
34.......
35.......
36.......
37.......
38.......
39.......
40.......
41.......
42C ......
43.......
44.......
45.......
46.......
47.......
48.......
49.......
50 .......
51 .......
52.......
53.......
Table 2 (continued)
TERATOMA INFORMATIVE HETEROMORPHISMS
CASE Karyotype Zygositya Number Chromosome number
54.46,XX + 3 9, 13, 14
55.46,XX - 4 13, 14, 15, 22
56.46,XX - 6 9, 13, 14, 15, 21, 22
57.46,XX - 4 3, 13, 14, 15
58.46,XX - 6 4, 9, 13, 14, 15, 22
59.46,XX + 3 14,15,22
60.46,XX + 4 4, 13, 14, 21
61.46,XX - 4 3, 9, 13, 21
62.46,XX + 3 14,15,22
63.46,XX + 5 3, 13, 14, 15, 22
64.46,XX + 5 13, 14, 15, 21, 22
65.46,XX + 4 3,13,15,22
66.46,XX - 3 1,9,15
67.46,XX + 7 3, 4, 9, 13, 14, 15, 22
68.47,XX,+8 - 4 9, 13, 15, 21
69.46,XX + 4 1, 9, 13, 14
70.46,XX - 4 3, 13, 14, 15
71.46,XX + 4 3,13,14,21
72.46,XX + 4 13, 14, 15, 16
73.46,XX - 2 3, 21
74.46,XX - 4 13, 14, 15, 21
75.46,XX - 2 13, 22
76.46,XX - 3 3,13,22
77.46,XX - 5 9, 13, 14, 15, 21
78.46,XX - 4 3,13,14,22
79. 48,XX,+7,+12 + 5 13, 14, 15, 21, 22
80.46,XX - 3 13, 21, 22
81.46,XX - 4 3,13,14,22
82.46,XX - 4 9, 13, 14, 21
83.46,XX - 7 4, 9, 13, 14, 15, 21, 22
84.46,XX + 4 3,13,14,22
85.46,XX - 3 3,13,14
86C 46,XX - 6 4, 13, 14, 15, 21, 22
87.46,XX - 3 9, 14, 21
88b ...... 46,XX - 4 3,4,13,22
89b. 47,XX,+15 - 4 3, 4, 13, 21
gob...... 46,XX NI
91b. 46,XX NI
92.46,XX NI
93.46,XX NI
94.46,XX NI
95.46,XX NI
96.46,XX NI
97.46,XX NI
98.46,XX NI
99.46,XX NI
100. 46,XX NI
101. 46,XX NI
102d 91,XXXX, - 13,mosaic NI
a + = Heterozygous; - = homozygous; NI = chromosomal hetermorphisms not informative.
b Bilateral cases.
c Malignant degeneration.
d 46,XX (11 cells)/91,XXXX, - 13 (33 cells)/93,XXXX, + 13 (3 cells).
641
Surti et al.
cells could be cytogenetically analyzed. Use of minisatel-
lite probes on frozen tissue as well as cultured cells can
also provide valuable additional information in differen-
tiating overall genetic identity of tumor and the host
tissue. Such studies have already begun in our labora-
tories, as is described in the companion paper (Deka
et al. 1990).
Chromosome heteromorphisms are not informative
in all cases, and scoring these markers can be subjec-
tive when the observable differences between the homo-
logues are minute. Thus, it seems necessary to use cen-
tromeric alpha satellite probes to provide additional
information on the centromeric zygosity (Willard et al.
1986).
Karyotypic results from the benign cases usually re-
vealed a normal 46,XX genotype; however, the data
also included four cases of trisomy (47,XXX,
47,XX,+ 8, 47,XX,+ 8, 47,XX,+15), one case of dou-
ble trisomy (47,XX,+7,+12), one case that involved
a trisomy and a structural rearrangement (47,XX,-15,
-21,+mar), and one case of tetraploidy in a mosaic
form. The incidence of chromosomal abnormality in
benign ovarian teratomas was found to be 7% in this
study. Tetraploidy and structural rearrangement in be-
nign ovarian teratoma have not been reported earlier
due to their low frequency. Our data also demonstrate
that ovarian teratomas are monoclonal in origin. Out
of 15 cases of trisomies and double trisomies reported
in mature and immature ovarian teratomas, five cases
have trisomy for chromosome 8. Trisomy 8 is one of
the most common trisomies observed in tumors. Three
cases each involve an additional X and 12 chromosome.
Out of six cases with trisomies detected in our study,
four have homozygous centromeric markers indicating
type II origin in four cases and type I or IV origin in
the remaining two cases (table 2). Only a few bilateral
and multiple cases have been analyzed so far and these
do not show preponderance of any one mechanism
within individuals (Carritt et al. 1982). The incidence
of chromosomal abnormalityin immature cases
(62.5%) seems to be much higher than in mature cases
(5%). (Patil et al. 1978; Ohama 1987; present study).
The 7% incidence of chromosomal abnormalities in
benign ovarian teratomas is less than the average 23%
(range 4.5%-47%) incidence of chromosomal abnor-
malities reported in oocytes from in vitro fertilization
patients (Ma et al. 1989). These two populations of
patients differ in many respects, including the age of
the patients, obstetric history, artificial induction of ovu-
lation, and selection of oocytes used for cytogenetic anal-
ysis, making the comparison difficult. The cases with
hyperhaploid oocytes do not show preponderance of
C group chromosomes as seen in ovarian teratomas.
The percentage of triploidy and tetraploidy cases in the
ovarian teratoma is also much less than the percentage
of diploid oocytes observed.
As with human ovarian teratomas, murine ovarian
teratomas have also been studied with respect to their
origin. Early studies (Eicher 1978; Eppig and Eicher
1983) utilized mouse ovarian teratomas as cytogenetic
tools for gene-centromere and gene-gene mapping. Par-
ticular mouse strains, such as LT/Sv and LTXBJ, have
an increased tendency to develop ovarian teratomas.
Therefore, these strains were used to determine mouse
gene-centromere distances. As was first thought with
human ovarian teratomas, mouse teratomas are believed
to arise from germ cells that have completed their first
meiotic division but failed to complete their second
meiotic division. On this assumption, mapping studies
were performed with the use of electrophoretic enzyme
polymorphisms. Eppig and Eicher (1983, 1988) com-
pared their results obtained from teratoma mapping
with the results from classical recombination analysis
and concluded that the two methods produce compara-
ble recombination frequencies in mice. Whereas human
ovarian teratomas are now believed to have multiple
mechanisms of origin, mouse ovarian teratomas are still
considered to result only from a meiosis II error. This
may be due to an inherent factor in the particular strains
of mice used in the study, or it may be that ovarian
teratomas in the mouse have one predominant mecha-
nism of origin. In light of the fact that all of the map-
ping data is based on the assumption that murine ovar-
ian teratomas develop due to a meiosis II error,
additional studies should be performed to test the va-
lidity of this assumption.
Recent studies in mouse as well as man indicate that
the presence of both female and male pronuclei is es-
sential for normal development (Searle et al. 1989).
Ovarian teratomas represent an interesting developmen-
tal anomaly of the germ cells in which the embryonic
differentiation begins prematurely without the input
from the paternal pronucleus and results in disorganized
mixture of mature tissues. Cultured cells available from
a large number of cytogenetically characterized human
teratomas can be used for further biochemical and de-
velopmental studies.
Acknowledgments
This work was supported in part by NIH grant CA43881
and by the Pathology Education and Research Foundation.
642
Chromosomal Origin of Ovarian Teratomas 643
A.C. was supported by NIH Research Career Development
award HD00774 and by NIH grant GM 33771. We thank
William Leger and Shubha Mullick for technical assistance
and Sally Derigo for typing the manuscript. We thank Dr.
Susan Shen for the tissue and information on immature ter-
atoma.
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