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Loss of the Y chromosome in gastric carcinoma. Fact or artifact?
234
Abstracts
36 ~ C ANALYSIS OF COLON G. Bardi, B. Johansson, C. 0rndal, S. Heim, N. Mandahl, N. Pandis, 7%. ~ - S a n d b e r g , and F. Mitelman. Departments of Clinical Genetics (G. B., B. J., C. O., S. H., N. M., N. P., F. M.) and Surgery (7%. A-S.), University Hospital, S-221 85 Iur~, Sweden. Short-term cultures of 26 a d e n o c a l ~ of the colon were examined. Because of infection, no outgrowth was obtained in three cases. Ten tumors had normal k a r y o ~ . Clonal ~ abnormalities were identified in thirteen tumors. In eight of them, only simple numerical changes were detected, qhree cases had triscmy 7 as the sole anomaly. Tne fourth tumor had one clone with loss of one X ~ and a second clone with loss of X, trisomy 6, and triscmy 7. Tne fifth tumor with numerical changes only had one clone with trisc~y 6 and trisc~y 12 and another with trisomy 12 as the sole a ~ m ~ l y . Finally, three tumors had loss of the Y chromosome as the only change. Structural as ~ell as numerical chromosomal aberrations were detected in five tumors. Tne modal ~ number was in the triploid range in four tumors and pseudodiploid in one; all had massive structural changes. ~ne short arm of 1 was involved in different aberrations in all five tumors, as rearrangement of band ip13 in two. Whereas the various structural abnormalities in the tumors with conplex karyotypes presumably contributed to the tumors' growth potential, the simple numerical changes that occurred clonally are more difficult to interpret. Both trisomy 7 and sex losses have been reported in nonneoplastic tissues. The question of whether the simple numerical cb_romoscm~ abnormalities found in colon c a r c ~ represent early genomic instability in the tumor parenchyma, are present in normal or at least nonneoplastic epithelial cells, or characterize s ~ fibroblasts, remains unresolved.
37 CYTOGENETIC AND MOLECULAR GENETIC STUDIES ON CARCINOMAS OF THE RECTUM AND COLON E. Gebhart*, D. Rau*, A. KSster**, G.v. Heimendahl**, T. Dingermann** * Institute of Human Genetics, ** Institute of Biochemistry,
S. Neubauer*, H. Tittelbach*, R. Sachse**,
Schwabachanlage Fahrstr.
10, d-8520 Erlangen, Germany
17, D-8520 Erlangen, Germany
A considerable heterogeneity of chromosome counts was found in surgical material obtained from 44 rectal and 22 colon carcinomas. The detailed karyotypic analysis of 24 of the former and 12 of the latter tumors revealed non-random patterns of chromosome abnormalities. While chromosomes no. 2, 3, 12, 20, and 22 were those most frequently involved in hypersomies and chromosomes 5, 14 and Y tended to monosomy in rectal tumors, nonrandom involvement in hypersomy was observed of chromosomes I, 6, 15, 20, 21, and X in colon tumors, and monosomies were found of chromosomes I, 12, 13, 15,18, X, and Y in this latter type of tumor. The chromosome arms non-randomly involved in marker formation were 17p, 3q, Ip, 7p, 14q, and 7q (in the order of decreasing frequency) in rectal, and 17p, 6q, Ip and q, and 7q in colon carcinomas. Using a cDNA dot blot technique and a battery of respective DNA probes, protooncog~ne expression was studied in a total of 53 rectal and 10 colon tumors, but also in a total of 12 samples of inconspicuous mucosae either taken distant to the tumor site, or from non-tumor patients. A combined overexpression of several proto-oncogenes was the most striking finding in cells of most tumor samples. The pattern of their combination proved to be non-
Abstracts
235
random. Most frequently overexpressed were the oncogenes of the ras family, but also fos and src. In the last phase of the study also a clear overexpression of the erb B (EGFR) gene was detected. In addition, some of the inconspicuous mucosae of tumor patients already exhibited clear signals of proto-oncogene overexpression, a finding which was lacking in mucosae of non-tumor patients. Study supported by grants of the Johannes and Frieda Marohn-Stiftung, Erlangen
38
RECURRENT DI
SEGNI
M.,
CHROM()SOMAL
BAROLI
TOMA, sezione di chirurg[ca,Cernusco
P.,
CHANGES
BISS[
O.*,
FROM MOR
20 COLOI{ECTAL C.*,and
citogen(~t ica , B u s t o Hul Navig| i o , M ~ l a n o .
A.
MAGGI -*[
TUMORS F.
divisiono
Twenty tumor s a m p l o s o b t a i n e d f r o m co]orect.al %~yops]es have b e e n cytogenetically studir,{l by direcl chromosrm, q a n a l y s i s . K a r y o t y p i n g was s u c c o s s f , l ly c a r r i e d out on ]3 t u m o r s (65%). Five of these, c a s e s s h o w o d a c h r o m o s o m e c o m p l e m e n t in the t r i p l o ] d or t e t r a p ] o J d r a n g e and w o r e not considere(] in this ~tudy. In the r e m a i n i g 8 n e a r - d i p l o i d c o l o r e c t a l tumors, cytogenet]cs analysis showed some chromosomes preferentially involved in structural rearrangements, partial or c o m p l e t e l o s s e s or gains. By o r d e r of decreasing f r e q u e n c y t h e s e were: chromosomes 17 ( 4 / 8 ) , 1 2 ( 4 / 8 ) , [ (3/8), 6 (3/8), 13 (3/8), 8 (2/8). A m o n g n u m e r i c a l c h a n g e s m o n o s o m y 17 and t r i s o m y X w e r e o b s e r v e d in two cases, r e s p e c t i v e l y . On the b a s i s of t h e s e r e s u l t s and o t h e r s p r e v i o u s l y reported in the literature, (1,2,3,4) we can c o n c l u d e that imbalance of chromosomes 17 and 12 are the m o s t f r e q u e n t f i n d i n g s . On the o t h e r hand it is not s p e c i f i c a ] [y o b s e r v e d ]n all c a s e s ; so we can suppose that change of c h r o m o s o m e s 17 and ]2 may reflect an i n t e r m e d i a t e s t e p in the k a r y o t y p i c e v o l u t i o n of this t u m o r r a t h e r than a p r i m a r y event. REFERENCES ] .
B e c h e r R, G i b a s Z, S a n d b e r g 7 A N D 12 IN LARGE DOWEL G e n e t C y t o g e n e t 9: 3 2 9 - 3 3 2 .
2.
O c h i H. , T a k e u c h i ,7. , lh)lyoke D. , S a n d b e r g AA. (]983) : P O S S I B L E S P E C I F I C CIIROMOSOME CIIAN(~E iN L A R G E B O W E L C A N C E R . Cancer Genet and Cytogenet 10:121-122
3.
MulerJs M. , S a l m o n R.J., D u t r i l l a u x A.M., V i e l h P.,Zafrani B.,Girodet J.,Dutrillaux B. (1988): C H A R A C T E R I S T I C CHROMOSOMAL I M B A L A N C E IN 18 N E A R - D I P L O I D C O L O R E C T A L T U M O R S . Cancer Genet and Cytogenet 29:289-301
4.
Y a s e e n N.Y., W a t m o r e A.E.,Potter and Rees R.C. (1989) : C H R O M O S O M E TUMORS
A A (198]): INVOI,VEMENT OF CEOM()SOME CANCEl{: Trisomy 7 and 12q Cancer
C.W., P o t t e r STUDIES IN
A.M.,Jacob G. ii COLORECTAL
Abstracts
36 ~ C ANALYSIS OF COLON G. Bardi, B. Johansson, C. 0rndal, S. Heim, N. Mandahl, N. Pandis, 7%. ~ - S a n d b e r g , and F. Mitelman. Departments of Clinical Genetics (G. B., B. J., C. O., S. H., N. M., N. P., F. M.) and Surgery (7%. A-S.), University Hospital, S-221 85 Iur~, Sweden. Short-term cultures of 26 a d e n o c a l ~ of the colon were examined. Because of infection, no outgrowth was obtained in three cases. Ten tumors had normal k a r y o ~ . Clonal ~ abnormalities were identified in thirteen tumors. In eight of them, only simple numerical changes were detected, qhree cases had triscmy 7 as the sole anomaly. Tne fourth tumor had one clone with loss of one X ~ and a second clone with loss of X, trisomy 6, and triscmy 7. Tne fifth tumor with numerical changes only had one clone with trisc~y 6 and trisc~y 12 and another with trisomy 12 as the sole a ~ m ~ l y . Finally, three tumors had loss of the Y chromosome as the only change. Structural as ~ell as numerical chromosomal aberrations were detected in five tumors. Tne modal ~ number was in the triploid range in four tumors and pseudodiploid in one; all had massive structural changes. ~ne short arm of 1 was involved in different aberrations in all five tumors, as rearrangement of band ip13 in two. Whereas the various structural abnormalities in the tumors with conplex karyotypes presumably contributed to the tumors' growth potential, the simple numerical changes that occurred clonally are more difficult to interpret. Both trisomy 7 and sex losses have been reported in nonneoplastic tissues. The question of whether the simple numerical cb_romoscm~ abnormalities found in colon c a r c ~ represent early genomic instability in the tumor parenchyma, are present in normal or at least nonneoplastic epithelial cells, or characterize s ~ fibroblasts, remains unresolved.
37 CYTOGENETIC AND MOLECULAR GENETIC STUDIES ON CARCINOMAS OF THE RECTUM AND COLON E. Gebhart*, D. Rau*, A. KSster**, G.v. Heimendahl**, T. Dingermann** * Institute of Human Genetics, ** Institute of Biochemistry,
S. Neubauer*, H. Tittelbach*, R. Sachse**,
Schwabachanlage Fahrstr.
10, d-8520 Erlangen, Germany
17, D-8520 Erlangen, Germany
A considerable heterogeneity of chromosome counts was found in surgical material obtained from 44 rectal and 22 colon carcinomas. The detailed karyotypic analysis of 24 of the former and 12 of the latter tumors revealed non-random patterns of chromosome abnormalities. While chromosomes no. 2, 3, 12, 20, and 22 were those most frequently involved in hypersomies and chromosomes 5, 14 and Y tended to monosomy in rectal tumors, nonrandom involvement in hypersomy was observed of chromosomes I, 6, 15, 20, 21, and X in colon tumors, and monosomies were found of chromosomes I, 12, 13, 15,18, X, and Y in this latter type of tumor. The chromosome arms non-randomly involved in marker formation were 17p, 3q, Ip, 7p, 14q, and 7q (in the order of decreasing frequency) in rectal, and 17p, 6q, Ip and q, and 7q in colon carcinomas. Using a cDNA dot blot technique and a battery of respective DNA probes, protooncog~ne expression was studied in a total of 53 rectal and 10 colon tumors, but also in a total of 12 samples of inconspicuous mucosae either taken distant to the tumor site, or from non-tumor patients. A combined overexpression of several proto-oncogenes was the most striking finding in cells of most tumor samples. The pattern of their combination proved to be non-
Abstracts
235
random. Most frequently overexpressed were the oncogenes of the ras family, but also fos and src. In the last phase of the study also a clear overexpression of the erb B (EGFR) gene was detected. In addition, some of the inconspicuous mucosae of tumor patients already exhibited clear signals of proto-oncogene overexpression, a finding which was lacking in mucosae of non-tumor patients. Study supported by grants of the Johannes and Frieda Marohn-Stiftung, Erlangen
38
RECURRENT DI
SEGNI
M.,
CHROM()SOMAL
BAROLI
TOMA, sezione di chirurg[ca,Cernusco
P.,
CHANGES
BISS[
O.*,
FROM MOR
20 COLOI{ECTAL C.*,and
citogen(~t ica , B u s t o Hul Navig| i o , M ~ l a n o .
A.
MAGGI -*[
TUMORS F.
divisiono
Twenty tumor s a m p l o s o b t a i n e d f r o m co]orect.al %~yops]es have b e e n cytogenetically studir,{l by direcl chromosrm, q a n a l y s i s . K a r y o t y p i n g was s u c c o s s f , l ly c a r r i e d out on ]3 t u m o r s (65%). Five of these, c a s e s s h o w o d a c h r o m o s o m e c o m p l e m e n t in the t r i p l o ] d or t e t r a p ] o J d r a n g e and w o r e not considere(] in this ~tudy. In the r e m a i n i g 8 n e a r - d i p l o i d c o l o r e c t a l tumors, cytogenet]cs analysis showed some chromosomes preferentially involved in structural rearrangements, partial or c o m p l e t e l o s s e s or gains. By o r d e r of decreasing f r e q u e n c y t h e s e were: chromosomes 17 ( 4 / 8 ) , 1 2 ( 4 / 8 ) , [ (3/8), 6 (3/8), 13 (3/8), 8 (2/8). A m o n g n u m e r i c a l c h a n g e s m o n o s o m y 17 and t r i s o m y X w e r e o b s e r v e d in two cases, r e s p e c t i v e l y . On the b a s i s of t h e s e r e s u l t s and o t h e r s p r e v i o u s l y reported in the literature, (1,2,3,4) we can c o n c l u d e that imbalance of chromosomes 17 and 12 are the m o s t f r e q u e n t f i n d i n g s . On the o t h e r hand it is not s p e c i f i c a ] [y o b s e r v e d ]n all c a s e s ; so we can suppose that change of c h r o m o s o m e s 17 and ]2 may reflect an i n t e r m e d i a t e s t e p in the k a r y o t y p i c e v o l u t i o n of this t u m o r r a t h e r than a p r i m a r y event. REFERENCES ] .
B e c h e r R, G i b a s Z, S a n d b e r g 7 A N D 12 IN LARGE DOWEL G e n e t C y t o g e n e t 9: 3 2 9 - 3 3 2 .
2.
O c h i H. , T a k e u c h i ,7. , lh)lyoke D. , S a n d b e r g AA. (]983) : P O S S I B L E S P E C I F I C CIIROMOSOME CIIAN(~E iN L A R G E B O W E L C A N C E R . Cancer Genet and Cytogenet 10:121-122
3.
MulerJs M. , S a l m o n R.J., D u t r i l l a u x A.M., V i e l h P.,Zafrani B.,Girodet J.,Dutrillaux B. (1988): C H A R A C T E R I S T I C CHROMOSOMAL I M B A L A N C E IN 18 N E A R - D I P L O I D C O L O R E C T A L T U M O R S . Cancer Genet and Cytogenet 29:289-301
4.
Y a s e e n N.Y., W a t m o r e A.E.,Potter and Rees R.C. (1989) : C H R O M O S O M E TUMORS
A A (198]): INVOI,VEMENT OF CEOM()SOME CANCEl{: Trisomy 7 and 12q Cancer
C.W., P o t t e r STUDIES IN
A.M.,Jacob G. ii COLORECTAL