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Incidence and origin of dicentric chromosomes in cultured meningiomas
Incidence and Origin of Dicentric Chromosomes in Cultured Meningiomas Juan A. Rey, M. Josefa Bello, Jose M. de Campos, and M. Elena Kusak
ABSTRACT: Based on the cytogenetic findings in 32 human meningiomas, an analysis of dicentric chromosomes, usually present in cultures from meningiomas, has been performed. The incidence and origin of such markers have been analyzed and the chromosomal composition of the stem line in the corresponding sample established (i.e., normal karyotype. - 2 2 as the sole chromosomal deviation, or complex karyotypes in addition to #22 abnormalities). More than 100 dicentric chromosomes were found in 12 of 32 meningiomas (37.5%). Sixty-eight of the markers could be identified individually or as belonging to a chromosome group. Fiftythree percent of the meningiomas characterized by a complex stem line karyotype also displayed dicentric chromosomes in variant cells, whereas only 12.5% of meningiomas with a normal diploid stem line showed such chromosomal aberrations. Chromosomes of groups C and D participated most frequently in the genesis of dicentrics; however, chromosomes 19, 20, 3, 6, and 13 were the most frequently involved. Thus, the existence of a nonrandom pattern of involvement supports the fact that dicentrics might play a biologic role in the progression of human meningiomas.
INTRODUCTION
Meningioma is a benign tumor characterized by special cytogenetic features. First, it shows a specific chromosomal change (partial deletion or m o n o s o m y of chromosome 22) [1-5]. Second, it frequently shows other clonal rearrangements (secondary to the #22 abnormalities) that seem to fit a pattern, i.e., loss of chromosomes 8, 14, and sex chromosomes, and structural changes involving chromosomes 1 (underrepresentation of the short arm with overrepresentation of the long arm), 7, and 11 (generally loss of 11p) [6-16]. Third, meningiomas constitute the only solid tumor in which clona] evolution starting with the primary chromosomal abnormality and subsequent superimposed aberrations can be followed and, thus, the various steps identified [10, 17]. In contrast to the benign behavior of most meningiomas, rings and, more frequently, dicentric marker chromosomes appear to characterize the cytogenetic evolution of these tumors. Whereas rings have been found to characterize ten tumor stem lines [7, 9, 14, 16, 18, 19], dicentric chromosomes generally are present in variant cells and are rarely reported as a clona] abnormality [11], although they can be found in up to 10% of the metaphases analyzed in some samples. From the Departmentof Genetics(J.A.R.,M.J.B.) and the Departmentof Neurosurgery{J.M.deC.,M.E.K.), EundacionJimenez Diaz, Madrid, Spain. Address requests for reprints to ]uan A. Rey, Department of Genetics, Fundacion ]imenez Diaz, Avda. Reyes Catolicos No. 2, 28040 Madrid, Spain. Received February 4, 1988; accepted May 16, 1988.
55 ¢3 J. A. Rev
Cancer Genet Cytogenet 35:55 60 (1988)
56
J.A. Rey et ah
Data on the incidence of dicentrics in meningiomas, their presence in relation to the stem line karyotype, and patterns of chromosome involvement are rarely reported. We present herein the results on these parameters concerning more than 100 dicentric markers present in a series of 32 meningiomas.
MATERIALS
AND
METHODS
The material consisted of 32 meningiomas in which direct preparations and/or in vitro cultures were performed to achieve cytogenetic studies. The methodology used was described previously [20]. The clinicopathologic data concerning the tumors and patients on which the present study is based were reported in detail elsewhere [16, 20]. In each sample, special attention was given to an evaluation of the presence of dicentric chromosomes in the stem line, side line, or variant cells. Banding analysis was performed whenever possible in order to identify the dicentric chromosomes.
RESULTS
The chromosomal characteristics regarding the stem and side lines of the 32 tumors have been reported previously in detail [16, 20]. One tumor (TS-18) was excluded in this study because only results by direct preparations were obtained. Table 1 shows the distribution and incidence of dicentric chromosomes in relation to the stem line karyotype of the tumors. Twelve of the 32 samples (37.5%) displayed dicentrics. They were m a i n l y present in variant cells; it was difficult to find two identical dicentrics, even in the same sample. Only two tumors (TS-114 and TS139) contained this type of marker chromosomes in the stem lines. Seven of the 12 tumors displaying dicentrics were characterized by stem lines with marker chromosomes (group I). In the other four tumors, the stem line showed m o n o s o m y 22 as the sole deviation (group II), whereas only one sample in eight displaying normal
Table 1
Group
Distribution and percentage of dicentric marker chromosomes according to the stem line karyotype in 31 cultured meningiomas
Stem line
Number of cases
Number of cases displaying dicentric markers
I
- 2 2 plus other alterations
13a
7
II
- 22
10
4
III
Normal karyotype
8
1
Cells with dicentric markers in each tumor (%) TS-12 (3.00) TS-35 (3.00) TS-66 (1.96) TS-74 (3.50) TS-139 (15.47) TS-171 (12.00) TS-175 (8.03) TS-80 (10.50) TS-88 (1.54) TS-95 (3.41) TS-164 (5.00) TS-101 (5.76)
aOne tumor (TS-18)belongingto this group has not been included because only direct preparations were successful.
57
Dicentrics in Meningioma
(diploid) stem line karyotypes (group III) included variant cells with dicentrics. Figure 1 illustrates a sample of dicentrics from variant cells of cultured meningiomas. As can be seen, dicentric markers generally originated by telomere-telomere fusion, without any apparent loss of material. However, isodicentrics and dicentrics, implicating loss of material, were occasionally found. Nevertheless, acentric fragments were not always present in these metaphases. Premature chromosome condensation (PCC) was found in less than 1% of the metaphases. It was present mainly in tumors from group I, was rarely present in those from group II, and no tumor from group III (characterized by a normal diploid stem line) exhibited PCC. In order to obtain an analysis of the chromosomes involved in the genesis of dicentrics in meningiomas, only those markers for which the participating chromosomes could be identified (individually or as belonging to a chromosome group) have been included. A total of 68 dicentrics were considered. Their distribution, according to the involved chromosomes, is shown in Table 2. Chromosomes from group C participated in the genesis of 41 of the 68 dicentrics. In three instances, the C group chromosome was identified by banding techniques as an X. Next in frequency were chromosomes from group D, which participated in the genesis of 25 markers. However only eight dicentrics due to C-D group translocations were found. The F group chromosomes were third in frequency, generating 21 dicentrics. When the involvement of individual chromosomes was estimated, #19 and #20 were the most frequent participants, followed by #3, #13, and #6, involved in seven, seven, and nine markers, respectively. Infrequently, tri- or tetracentric marker chromosomes were also found. However, their pattern of involvement did not seem to differ from that found for dicentrics. Figure 1
Some dicentric chromosomes found in cultured meningiomas.
W
6;?;15
t 15;?
13;19
6;9
3;16
7;7
7;19
i ii iil''
8;11
9;x
6;20
6;13
1;6
11;15
11;?
9;19
8;17
i 10;17
9;14
tetracentric
58
I.A. Rey et al.
Distribution of dicentric markers according to the chromosomes involved
Table 2
1 2 3 4 5 C D 16 17 18 F G X ?
1
2
3
1 1
1
2 2 2
1
4
5
1
1 1
c
7 8 4 2 1 7 4 3 1
D
16
17
18
F
G
1 1 8 2
1 2
2
1
No relation between the age of the patients and the presence of dicentrics could be established. Ten of the 12 tumors displaying such rearrangements originated from female patients. Also, as has been pointed out, an increased t e n d e n c y toward the development of variant cells with dicentrics in relation to a more complex tumor karyotype was evident.
DISCUSSION
The presence of dicentrics in cultures derived from h u m a n meningiomas has been reported previously. Data on the subject are available from only two large series on the cytogenetic findings in meningiomas [7, 11]. Mark [7] reported the presence of dicentrics in side lines of two cases (no case displaying such abnormality in the stem line was included); they were also present in variant cells of 11 (of 50} additional at the first preparation (primary culture). However, as reported by Mark, dicentrics could be seen in variant cells from all meningiomas placed in long-term culture. As we reported previously [16, 20], the in vitro culture periods for m e n i n g i o m a s on which our findings are based were highly variable from case to case, up to 43 days of in vitro propagation (equivalent to six passages) in a few cases. For a given tumor, however, the presence or absence of dicentric chromosomes was definitive from primary cultures. This characteristic was unchanged with longer periods of growth in vitro. In fact, we have not found any tumor without dicentric markers in early studies and displaying them in advanced passages. Also, no variation was found in the frequency of such markers parallel to an increase of the time of growth in vitro. Our results have shown an increase in the frequency of tumors displaying dicentrics in accordance with a more complex stem line karyotype. Whereas only one of eight tumors with a normal (diploid) stem line (group III) displayed dicentrics in variant cells, seven of 14 samples in group I (i.e., those tumors with other anomalies in additon to - 2 2 ) i n c l u d e d such abnormalities. This fact might reflect a chromosomal instability contributing to the genesis of other rearrangements, perhaps related to the evolutionary advantage for the in vitro progression of meningiomas.
Dicentrics in Meningioma
59
However, dicentric chromosomes can be seen in the primary cultures of some tumors, perhaps as a result of conditions in vivo. These data are in agreement with those reported by Zang [11], who showed a significant increase of dicentrics in meningiomas characterized by 40-44 chromosomes in relation to those displaying either a normal karyotype or only monosomy 22. Parallel to this increase, Zang [11] found an increase in the frequency of breaks in the same tumor groups. This aspect could not be tested in our series due to its low incidence. However, in some tumors we found PCC, another possible expression of a virus i n v o l v e m e n t in the etiology of some meningiomas. As reported earlier by Zang [11], dicentrics rarely occur uniformly in a cell line. We only found dicentric markers as part of stem or side lines in two tumors. According to the data recently provided by Vig and Zinkowski [21], a m e c h a n i s m exists for an orderly separation of dicentrics in mitosis, which enhance their stability and, thus, their presence es part of a given cell line. Data about the pattern of involvement of chromosome groups in the genesis of dicentrics in m e n i n g i o m a s [7, 11] show F group chromosomes to be the most frequently rearranged, generally due to translocations between F and G group chromosomes and, less frequently, A and F or C and F rearrangement. Chromosomes from group C would be next in frequency. In our series, two F - G dicentrics were seen, and the frequent i n v o l v e m e n t of F group chromosomes was m a i n l y due to C - F or D - F group translocations. Although chromosomes from group C were involved in the genesis of dicentrics most frequently, no particular chromosome seemed to be responsible for this i n v o l v e m e n t with the exception of chromosome 6. Chromosomes 3 and 13 were frequently involved, being m a i n l y responsible for the involvement of A and D group chromosomes. This pattern of chromosomal i n v o l v e m e n t does not agree with the pattern of clonal chromosomal abnormalities present in meningiomas. In fact, recent data have shown numerical deviations involving # 8 and #14 and rearrangements of l p and 11p as secondary aberrations to m o n o s o m y 22 [7, 9, 14, 16, 18, 19]. Thus, the genesis of dicentric chromosomes in meningiomas does not seem to be related to the genesis of clonal chromosomal abnormalities. However, the existence of a nonr a n d o m pattern of i n v o l v e m e n t of certain chromosomes (F group chromosomes, 3, 6, and 13) supports the fact that dicentrics might play a role in the tumoral progression of m e n i n g i o m a s and are not a fortuitous event. Supported by Grant 1170 from Comision Asesora para la Investigacion Cientifica y Tecnica (CAICYT), and by Fundacion Conchita Rabago de Jimenez Diaz.
REFERENCES 1. Mark J, Levan G, Mitelman F (1972): Identification by fluorescence of the G chromosome lost in human meningiomas. Hereditas 71:162-168. 2. Mark J, Mitelman F, Levan G (1972): On the specificity of the G abnormality in human meningiomas studied by the fluorescence technique. Acta Pathol Microbiol Scand, Sect A 80:812-820. 3. Zankl H, Zang KD (1971): Cytological and cytogenetical studies on brain tumors. Ill. Ph like chromosomes in human meningiomas. Hum Genet 12:42-49. 4. Zankl H, Weiss AF, Zang KD (1975): Cytological and cytogenetical studies on brain tumors. VI. No evidence for a translocation in 22 monosomic meningiomas. Hum Genet 30:343-348.
60
J.A.
Rey et al.
5. Zankl H, Zang KD (1972): Cytological and cytogenetical studies on brain tumors. IV. Identification of the missing G chromosome in h u m a n meningiomas as no. 22 by fluorescence technique. Hum Genet 14:167-169. 6. Mark J (1970): Chromosomal patterns in meningiomas. Eur J Cancer 6:489-498. 7. Mark J (1974): The h u m a n meningioma: a benign tumor with specific chromosome characteristics. In: Chromosomes and Cancer. John Wiley and Sons, NY, pp. 497-512. 8. Zang KD, Singer H (1967): Chromosomal constitution of meningiomas. Nature 216:84-85. 9. Mark J (1973): Karyotype patterns in h u m a n meningiomas. A comparison between studies with G- and Q-banding techniques. Hereditas 75:213-220. 10. Mark J (1977): Chromosomal abnormalities and their specificity in h u m a n neoplasms: an assessment of recent observations by banding techniques. Adv Cancer Res 24:165-222. 11. Zang KD (1982): Cytological and cytogenetical studies on h u m a n meningioma. Cancer Genet Cytogenet 6:249-274. 12. Yamada K, Kondo T, Yoshioka M, Oami H (1980): Cytogenetic studies in twenty h u m a n brain tumors: association of no. 22 chromosome abnormalities with tumors of the brain. Cancer Genet Cytogenet 2:293-307. 13. Katsuyama J, Papenhausen PR, Herz F, Gazivoda P, Hirano A, Koss LG (1986): Chromosome abnormalities in meningiomas. Cancer Genet Cytogenet 22:63-68. 14. A1 Saadi A, Latimer F, Madercic M, Robbins T (1987): Cytogenetic studies of h u m a n brain tumors and their clinical significance. II. Meningioma. Cancer Genet Cytogenet 26:127141. 15. Casalone R, Granata P, Simi P, Tarantino E, Butti G, Buonaguidi R, Faggiomato F, Knerich R, Solero L (1987): Recessive cancer genes in meningiomas? An analysis of 31 cases. Cancer Genet Cytogenet 27:145-149. 16. Rey JA, Bello MJ, de Campos, JM, Kusak ME, Moreno S (1988): Chromosomal involvement secondary to - 22 in h u m a n meningiomas. Cancer Genet Cytogenet (in press) 17. Sandberg AA (1980): The Chromosomes in Human Cancer and Leukemia. Elsevier North Holland, NY, pp. 535-543. 18. Mark J (1971): Chromosomal aberrations and their relation to malignancy in meningiomas: a meningioma with ring chromosomes. Acta Pathol Microbiol Scand, Sect A 79:193-200. I 19. Mark J (1973): Origin of the ring chromosome in a h u m a n recurrent meningioma studied with G-band technique. Acta Pathol Microbiol Scand, Sect A 81:588-590. 20. Rey JA, Bello MJ, de Campos JM, Benitez J, Ayuso MC, Valcarcel E (1983): Chromosome studies in two h u m a n brain tumors. Cancer Genet Cytogenet 10:159-165. 21. Vig BK, Zinkowski RP (1986): Sequence of centromere separation: a mechanism for orderly separation of dicentrics. Cancer Genet Cytogenet 22:347-359.
ABSTRACT: Based on the cytogenetic findings in 32 human meningiomas, an analysis of dicentric chromosomes, usually present in cultures from meningiomas, has been performed. The incidence and origin of such markers have been analyzed and the chromosomal composition of the stem line in the corresponding sample established (i.e., normal karyotype. - 2 2 as the sole chromosomal deviation, or complex karyotypes in addition to #22 abnormalities). More than 100 dicentric chromosomes were found in 12 of 32 meningiomas (37.5%). Sixty-eight of the markers could be identified individually or as belonging to a chromosome group. Fiftythree percent of the meningiomas characterized by a complex stem line karyotype also displayed dicentric chromosomes in variant cells, whereas only 12.5% of meningiomas with a normal diploid stem line showed such chromosomal aberrations. Chromosomes of groups C and D participated most frequently in the genesis of dicentrics; however, chromosomes 19, 20, 3, 6, and 13 were the most frequently involved. Thus, the existence of a nonrandom pattern of involvement supports the fact that dicentrics might play a biologic role in the progression of human meningiomas.
INTRODUCTION
Meningioma is a benign tumor characterized by special cytogenetic features. First, it shows a specific chromosomal change (partial deletion or m o n o s o m y of chromosome 22) [1-5]. Second, it frequently shows other clonal rearrangements (secondary to the #22 abnormalities) that seem to fit a pattern, i.e., loss of chromosomes 8, 14, and sex chromosomes, and structural changes involving chromosomes 1 (underrepresentation of the short arm with overrepresentation of the long arm), 7, and 11 (generally loss of 11p) [6-16]. Third, meningiomas constitute the only solid tumor in which clona] evolution starting with the primary chromosomal abnormality and subsequent superimposed aberrations can be followed and, thus, the various steps identified [10, 17]. In contrast to the benign behavior of most meningiomas, rings and, more frequently, dicentric marker chromosomes appear to characterize the cytogenetic evolution of these tumors. Whereas rings have been found to characterize ten tumor stem lines [7, 9, 14, 16, 18, 19], dicentric chromosomes generally are present in variant cells and are rarely reported as a clona] abnormality [11], although they can be found in up to 10% of the metaphases analyzed in some samples. From the Departmentof Genetics(J.A.R.,M.J.B.) and the Departmentof Neurosurgery{J.M.deC.,M.E.K.), EundacionJimenez Diaz, Madrid, Spain. Address requests for reprints to ]uan A. Rey, Department of Genetics, Fundacion ]imenez Diaz, Avda. Reyes Catolicos No. 2, 28040 Madrid, Spain. Received February 4, 1988; accepted May 16, 1988.
55 ¢3 J. A. Rev
Cancer Genet Cytogenet 35:55 60 (1988)
56
J.A. Rey et ah
Data on the incidence of dicentrics in meningiomas, their presence in relation to the stem line karyotype, and patterns of chromosome involvement are rarely reported. We present herein the results on these parameters concerning more than 100 dicentric markers present in a series of 32 meningiomas.
MATERIALS
AND
METHODS
The material consisted of 32 meningiomas in which direct preparations and/or in vitro cultures were performed to achieve cytogenetic studies. The methodology used was described previously [20]. The clinicopathologic data concerning the tumors and patients on which the present study is based were reported in detail elsewhere [16, 20]. In each sample, special attention was given to an evaluation of the presence of dicentric chromosomes in the stem line, side line, or variant cells. Banding analysis was performed whenever possible in order to identify the dicentric chromosomes.
RESULTS
The chromosomal characteristics regarding the stem and side lines of the 32 tumors have been reported previously in detail [16, 20]. One tumor (TS-18) was excluded in this study because only results by direct preparations were obtained. Table 1 shows the distribution and incidence of dicentric chromosomes in relation to the stem line karyotype of the tumors. Twelve of the 32 samples (37.5%) displayed dicentrics. They were m a i n l y present in variant cells; it was difficult to find two identical dicentrics, even in the same sample. Only two tumors (TS-114 and TS139) contained this type of marker chromosomes in the stem lines. Seven of the 12 tumors displaying dicentrics were characterized by stem lines with marker chromosomes (group I). In the other four tumors, the stem line showed m o n o s o m y 22 as the sole deviation (group II), whereas only one sample in eight displaying normal
Table 1
Group
Distribution and percentage of dicentric marker chromosomes according to the stem line karyotype in 31 cultured meningiomas
Stem line
Number of cases
Number of cases displaying dicentric markers
I
- 2 2 plus other alterations
13a
7
II
- 22
10
4
III
Normal karyotype
8
1
Cells with dicentric markers in each tumor (%) TS-12 (3.00) TS-35 (3.00) TS-66 (1.96) TS-74 (3.50) TS-139 (15.47) TS-171 (12.00) TS-175 (8.03) TS-80 (10.50) TS-88 (1.54) TS-95 (3.41) TS-164 (5.00) TS-101 (5.76)
aOne tumor (TS-18)belongingto this group has not been included because only direct preparations were successful.
57
Dicentrics in Meningioma
(diploid) stem line karyotypes (group III) included variant cells with dicentrics. Figure 1 illustrates a sample of dicentrics from variant cells of cultured meningiomas. As can be seen, dicentric markers generally originated by telomere-telomere fusion, without any apparent loss of material. However, isodicentrics and dicentrics, implicating loss of material, were occasionally found. Nevertheless, acentric fragments were not always present in these metaphases. Premature chromosome condensation (PCC) was found in less than 1% of the metaphases. It was present mainly in tumors from group I, was rarely present in those from group II, and no tumor from group III (characterized by a normal diploid stem line) exhibited PCC. In order to obtain an analysis of the chromosomes involved in the genesis of dicentrics in meningiomas, only those markers for which the participating chromosomes could be identified (individually or as belonging to a chromosome group) have been included. A total of 68 dicentrics were considered. Their distribution, according to the involved chromosomes, is shown in Table 2. Chromosomes from group C participated in the genesis of 41 of the 68 dicentrics. In three instances, the C group chromosome was identified by banding techniques as an X. Next in frequency were chromosomes from group D, which participated in the genesis of 25 markers. However only eight dicentrics due to C-D group translocations were found. The F group chromosomes were third in frequency, generating 21 dicentrics. When the involvement of individual chromosomes was estimated, #19 and #20 were the most frequent participants, followed by #3, #13, and #6, involved in seven, seven, and nine markers, respectively. Infrequently, tri- or tetracentric marker chromosomes were also found. However, their pattern of involvement did not seem to differ from that found for dicentrics. Figure 1
Some dicentric chromosomes found in cultured meningiomas.
W
6;?;15
t 15;?
13;19
6;9
3;16
7;7
7;19
i ii iil''
8;11
9;x
6;20
6;13
1;6
11;15
11;?
9;19
8;17
i 10;17
9;14
tetracentric
58
I.A. Rey et al.
Distribution of dicentric markers according to the chromosomes involved
Table 2
1 2 3 4 5 C D 16 17 18 F G X ?
1
2
3
1 1
1
2 2 2
1
4
5
1
1 1
c
7 8 4 2 1 7 4 3 1
D
16
17
18
F
G
1 1 8 2
1 2
2
1
No relation between the age of the patients and the presence of dicentrics could be established. Ten of the 12 tumors displaying such rearrangements originated from female patients. Also, as has been pointed out, an increased t e n d e n c y toward the development of variant cells with dicentrics in relation to a more complex tumor karyotype was evident.
DISCUSSION
The presence of dicentrics in cultures derived from h u m a n meningiomas has been reported previously. Data on the subject are available from only two large series on the cytogenetic findings in meningiomas [7, 11]. Mark [7] reported the presence of dicentrics in side lines of two cases (no case displaying such abnormality in the stem line was included); they were also present in variant cells of 11 (of 50} additional at the first preparation (primary culture). However, as reported by Mark, dicentrics could be seen in variant cells from all meningiomas placed in long-term culture. As we reported previously [16, 20], the in vitro culture periods for m e n i n g i o m a s on which our findings are based were highly variable from case to case, up to 43 days of in vitro propagation (equivalent to six passages) in a few cases. For a given tumor, however, the presence or absence of dicentric chromosomes was definitive from primary cultures. This characteristic was unchanged with longer periods of growth in vitro. In fact, we have not found any tumor without dicentric markers in early studies and displaying them in advanced passages. Also, no variation was found in the frequency of such markers parallel to an increase of the time of growth in vitro. Our results have shown an increase in the frequency of tumors displaying dicentrics in accordance with a more complex stem line karyotype. Whereas only one of eight tumors with a normal (diploid) stem line (group III) displayed dicentrics in variant cells, seven of 14 samples in group I (i.e., those tumors with other anomalies in additon to - 2 2 ) i n c l u d e d such abnormalities. This fact might reflect a chromosomal instability contributing to the genesis of other rearrangements, perhaps related to the evolutionary advantage for the in vitro progression of meningiomas.
Dicentrics in Meningioma
59
However, dicentric chromosomes can be seen in the primary cultures of some tumors, perhaps as a result of conditions in vivo. These data are in agreement with those reported by Zang [11], who showed a significant increase of dicentrics in meningiomas characterized by 40-44 chromosomes in relation to those displaying either a normal karyotype or only monosomy 22. Parallel to this increase, Zang [11] found an increase in the frequency of breaks in the same tumor groups. This aspect could not be tested in our series due to its low incidence. However, in some tumors we found PCC, another possible expression of a virus i n v o l v e m e n t in the etiology of some meningiomas. As reported earlier by Zang [11], dicentrics rarely occur uniformly in a cell line. We only found dicentric markers as part of stem or side lines in two tumors. According to the data recently provided by Vig and Zinkowski [21], a m e c h a n i s m exists for an orderly separation of dicentrics in mitosis, which enhance their stability and, thus, their presence es part of a given cell line. Data about the pattern of involvement of chromosome groups in the genesis of dicentrics in m e n i n g i o m a s [7, 11] show F group chromosomes to be the most frequently rearranged, generally due to translocations between F and G group chromosomes and, less frequently, A and F or C and F rearrangement. Chromosomes from group C would be next in frequency. In our series, two F - G dicentrics were seen, and the frequent i n v o l v e m e n t of F group chromosomes was m a i n l y due to C - F or D - F group translocations. Although chromosomes from group C were involved in the genesis of dicentrics most frequently, no particular chromosome seemed to be responsible for this i n v o l v e m e n t with the exception of chromosome 6. Chromosomes 3 and 13 were frequently involved, being m a i n l y responsible for the involvement of A and D group chromosomes. This pattern of chromosomal i n v o l v e m e n t does not agree with the pattern of clonal chromosomal abnormalities present in meningiomas. In fact, recent data have shown numerical deviations involving # 8 and #14 and rearrangements of l p and 11p as secondary aberrations to m o n o s o m y 22 [7, 9, 14, 16, 18, 19]. Thus, the genesis of dicentric chromosomes in meningiomas does not seem to be related to the genesis of clonal chromosomal abnormalities. However, the existence of a nonr a n d o m pattern of i n v o l v e m e n t of certain chromosomes (F group chromosomes, 3, 6, and 13) supports the fact that dicentrics might play a role in the tumoral progression of m e n i n g i o m a s and are not a fortuitous event. Supported by Grant 1170 from Comision Asesora para la Investigacion Cientifica y Tecnica (CAICYT), and by Fundacion Conchita Rabago de Jimenez Diaz.
REFERENCES 1. Mark J, Levan G, Mitelman F (1972): Identification by fluorescence of the G chromosome lost in human meningiomas. Hereditas 71:162-168. 2. Mark J, Mitelman F, Levan G (1972): On the specificity of the G abnormality in human meningiomas studied by the fluorescence technique. Acta Pathol Microbiol Scand, Sect A 80:812-820. 3. Zankl H, Zang KD (1971): Cytological and cytogenetical studies on brain tumors. Ill. Ph like chromosomes in human meningiomas. Hum Genet 12:42-49. 4. Zankl H, Weiss AF, Zang KD (1975): Cytological and cytogenetical studies on brain tumors. VI. No evidence for a translocation in 22 monosomic meningiomas. Hum Genet 30:343-348.
60
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Rey et al.
5. Zankl H, Zang KD (1972): Cytological and cytogenetical studies on brain tumors. IV. Identification of the missing G chromosome in h u m a n meningiomas as no. 22 by fluorescence technique. Hum Genet 14:167-169. 6. Mark J (1970): Chromosomal patterns in meningiomas. Eur J Cancer 6:489-498. 7. Mark J (1974): The h u m a n meningioma: a benign tumor with specific chromosome characteristics. In: Chromosomes and Cancer. John Wiley and Sons, NY, pp. 497-512. 8. Zang KD, Singer H (1967): Chromosomal constitution of meningiomas. Nature 216:84-85. 9. Mark J (1973): Karyotype patterns in h u m a n meningiomas. A comparison between studies with G- and Q-banding techniques. Hereditas 75:213-220. 10. Mark J (1977): Chromosomal abnormalities and their specificity in h u m a n neoplasms: an assessment of recent observations by banding techniques. Adv Cancer Res 24:165-222. 11. Zang KD (1982): Cytological and cytogenetical studies on h u m a n meningioma. Cancer Genet Cytogenet 6:249-274. 12. Yamada K, Kondo T, Yoshioka M, Oami H (1980): Cytogenetic studies in twenty h u m a n brain tumors: association of no. 22 chromosome abnormalities with tumors of the brain. Cancer Genet Cytogenet 2:293-307. 13. Katsuyama J, Papenhausen PR, Herz F, Gazivoda P, Hirano A, Koss LG (1986): Chromosome abnormalities in meningiomas. Cancer Genet Cytogenet 22:63-68. 14. A1 Saadi A, Latimer F, Madercic M, Robbins T (1987): Cytogenetic studies of h u m a n brain tumors and their clinical significance. II. Meningioma. Cancer Genet Cytogenet 26:127141. 15. Casalone R, Granata P, Simi P, Tarantino E, Butti G, Buonaguidi R, Faggiomato F, Knerich R, Solero L (1987): Recessive cancer genes in meningiomas? An analysis of 31 cases. Cancer Genet Cytogenet 27:145-149. 16. Rey JA, Bello MJ, de Campos, JM, Kusak ME, Moreno S (1988): Chromosomal involvement secondary to - 22 in h u m a n meningiomas. Cancer Genet Cytogenet (in press) 17. Sandberg AA (1980): The Chromosomes in Human Cancer and Leukemia. Elsevier North Holland, NY, pp. 535-543. 18. Mark J (1971): Chromosomal aberrations and their relation to malignancy in meningiomas: a meningioma with ring chromosomes. Acta Pathol Microbiol Scand, Sect A 79:193-200. I 19. Mark J (1973): Origin of the ring chromosome in a h u m a n recurrent meningioma studied with G-band technique. Acta Pathol Microbiol Scand, Sect A 81:588-590. 20. Rey JA, Bello MJ, de Campos JM, Benitez J, Ayuso MC, Valcarcel E (1983): Chromosome studies in two h u m a n brain tumors. Cancer Genet Cytogenet 10:159-165. 21. Vig BK, Zinkowski RP (1986): Sequence of centromere separation: a mechanism for orderly separation of dicentrics. Cancer Genet Cytogenet 22:347-359.