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52 Karyotypic and molecular analyses of colon cancer
42 51 ,
M Y O M A OF THE U T E R U S W I T H A C O M P L E X CHROMOSOME REARRANGEMENT. Z. Gibas*, C.A. G r i f f i n * * , and B.S. Emanuel**, Department of Pathology, The Medical College of P e n n s y l v a n i a * , D e p a r t m e n t of Pediatrics and Genetics, The Children's H o s p i t a l of Philadelphia**, Philadelphia, PA. Chromosome s t u d i e s w e r e p e r f o r m e d after short t e r m c u l t u r e of a m y o m a of uterus which showed extensive hyaline, myxoid and cystic degeneration. The tumor was histologically benign. Cytogenetic analysis r e v e a l e d a c l o n a l p o p u l a t i o n of cells w i t h m o d a l c h r o m o s o m e n u m b e r of 45, c o n s i s t e n t monosomy #22 a n d a c o m p l e x structural rearrangement involving chromosomes #3, #12, #14, #17, and #22. T h e k a r y o t y p e of the tumor was interpreted as 4 5 , X X , - 2 2 , t(3; 17) (p21;pl1.2) ,t (12;22) (q15;q13) ,del (14) (qll.2;q22). Metaphases w i t h n o r m a l f e m a l e karyotype were also obtained from the tumor. Cytogenetic study of seven additional myomas of the u t e r u s o b t a i n e d f r o m four p a t i e n t s showed normal female karyotype in a l l tumors. Single metaphases with a trisomy and a t r a n s l o c a t i o n w e r e d e t e c t e d in t w o tumors; the r e m a i n i n g t u m o r s s h o w e d o n l y normal cells with occasional random loss of chromosomes. W e conclude that while many uterine myomas a p p e a r to have n o r m a l k a r y o t y p e s , clonal chromosome abnormalities are present in some of these tumors. The s t u d y of c h r o m o s o m e rearrangements in b e n i g n t u m o r s m a y be helpful in d e f i n i n g chromosome regions a s s o c i a t e d w i t h a b n o r m a l p r o l i f e r a t i o n of cells. Supported in part by NCI grant CA-14137.
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KARIOTYPIC ~ D M O L E C U L A B ~ I S K S OF COLON ~CAM~B, S. Untawale, M. Blick, and S. Pathak. The University of Texas M.D. Anderson Hospital at Houston. To determine whether a correlation exists between chromosomal anomalies and altered oncogene expression in human colon cancer, we analyzed the karyotypes of 7 colon cancer cell lines utilizing Q- and G-banding. Although chromosome abnormalities were varied, chromosome 7 appeared to be present in increased number or was involved in rearrangements in each of the lines. Poly(A)+ RNA was extracted from these 7 cell lines, as well as from 6 fresh colon tumors. The mRNA was examined by Northern blot analyses utilizing probes for c-k-ras, c-myc, e-myb, c-fo__~s, c-erb--H, TGFand P53. Together with the Northern analyses, dot blot studies of total RNA from 9 additional fresh tumor tissues demonstrated low levels of expression in both cell lines and fresh tissue using 6 of the probes. However, enhanced c-myc expression was observed in a number of cell lines as well as in fresh tissue. Southern blot analysis revealed amplification of c-myc in 3 of the 7 cell lines. Aberrant expression itself was not associated directly with any chromosome anomalies. Nevertheless, chromosome 7 may prove to be a target towards which future cytogenetie and molecular studies of fresh colon tumors should be directed. The gene c-myc may in turn prove to have some particular significance in colon cancer as it demonstrated the highest levels of expression in both cell lines and fresh tissue. (Supported by PHS grant number CA09299-07, awarded by the NCI, DHHS).
53 *A CYTOGENETIC STUDY OF HUMAN PRIMARY BREAST TUMOR AND NONMALIGANT BREAST TISSUE. Jin S. Lee, Vicki Hopwood, Barbara Tomasovic, Gabriel Hortobagyi, Gary Spitzer, and Sen Pathak. U.T.M.D. Anderson Hospital, 6723 Bertner, Houston, Texas 77030. A cytogenetic study was carried out on 10 primary tumor and 9 nonmalignant breast tissue samples from 11 pts with primary breast cancer after culturing them for 2 wks using the adhesive tumor cell culture system (Cancer Res 46:1263, 1986). Up to 60 metaphase spreads were analyzed after G- or Q-banding. A modal chromosome number was 46. Chromosomes 1,4,5,7,8,12,14,18, and X were frequently involved in numerical or structural alterations. Clonal chromosomal abnormalities were seen in 4 tumor and 3 breast tissue samples. Of these, trisomy 7 was seen in I tumor and breast tissue from the same pt; trisomies 7 and 20 in I tumor; trisomy 8 in I tumor; trisomy 8 a n d t(4;4) in I breast tissue; trisomy 12 in I tumor; inv(1) and t(5;7) in I breast tissue. There was a suggestion of clonal evolution from normal breast tissue to tumor and within breast tumor itself. Further studies are in progress to correlate these cytogenetie data and other biological and clinical variables.
54
* CYTOGENETIC EVOLUTION IN HUMAN OVARIAN CARCINOMA: A SIMPLE METHOD FOR COMPARATIVE ANALYSES. Cynthia G. Roberts and Martin H.N. Tattersal], Ludwig Institute for Cancer Research (Sydney Branch), University of Sydney, Sydney, N.S.W. 2006, AUSTRALIA. Cytogenetic studies of solid tumor tissue are not only confounded by the technical difficulties encountered in their preparation, but also by the high level of karyotypic heterogeneity revealed. This marked heterogeneity results from both the sequential selection of mutant subpopulations involved in tumor progression as well as random changes. Tabular listings of karyotypiu changes provide a wealth of information about the degree of genetic instability of a tumor but are difficult to analyse, especially for comparative studies. One method of analysis is the ordering of identified chromosomal rearrangements according to their observed frequency and relationship to each other. In this way a pattern of clonal evolution may be inferred. Using this method of analysis on a serous ovarian carcinoma from 3 sites in the same patient, we were able to develop a pattern of cytogenetic evolution which may reflect the development of the tumor in vivo. Analysis by this method allows for comparative studies between different metastatic sites whthin the same tumor or of different patients with similar tumor type. Moreover, it may lead to the identification of specific chromosomal changes in tumor development.
M Y O M A OF THE U T E R U S W I T H A C O M P L E X CHROMOSOME REARRANGEMENT. Z. Gibas*, C.A. G r i f f i n * * , and B.S. Emanuel**, Department of Pathology, The Medical College of P e n n s y l v a n i a * , D e p a r t m e n t of Pediatrics and Genetics, The Children's H o s p i t a l of Philadelphia**, Philadelphia, PA. Chromosome s t u d i e s w e r e p e r f o r m e d after short t e r m c u l t u r e of a m y o m a of uterus which showed extensive hyaline, myxoid and cystic degeneration. The tumor was histologically benign. Cytogenetic analysis r e v e a l e d a c l o n a l p o p u l a t i o n of cells w i t h m o d a l c h r o m o s o m e n u m b e r of 45, c o n s i s t e n t monosomy #22 a n d a c o m p l e x structural rearrangement involving chromosomes #3, #12, #14, #17, and #22. T h e k a r y o t y p e of the tumor was interpreted as 4 5 , X X , - 2 2 , t(3; 17) (p21;pl1.2) ,t (12;22) (q15;q13) ,del (14) (qll.2;q22). Metaphases w i t h n o r m a l f e m a l e karyotype were also obtained from the tumor. Cytogenetic study of seven additional myomas of the u t e r u s o b t a i n e d f r o m four p a t i e n t s showed normal female karyotype in a l l tumors. Single metaphases with a trisomy and a t r a n s l o c a t i o n w e r e d e t e c t e d in t w o tumors; the r e m a i n i n g t u m o r s s h o w e d o n l y normal cells with occasional random loss of chromosomes. W e conclude that while many uterine myomas a p p e a r to have n o r m a l k a r y o t y p e s , clonal chromosome abnormalities are present in some of these tumors. The s t u d y of c h r o m o s o m e rearrangements in b e n i g n t u m o r s m a y be helpful in d e f i n i n g chromosome regions a s s o c i a t e d w i t h a b n o r m a l p r o l i f e r a t i o n of cells. Supported in part by NCI grant CA-14137.
52
KARIOTYPIC ~ D M O L E C U L A B ~ I S K S OF COLON ~CAM~B, S. Untawale, M. Blick, and S. Pathak. The University of Texas M.D. Anderson Hospital at Houston. To determine whether a correlation exists between chromosomal anomalies and altered oncogene expression in human colon cancer, we analyzed the karyotypes of 7 colon cancer cell lines utilizing Q- and G-banding. Although chromosome abnormalities were varied, chromosome 7 appeared to be present in increased number or was involved in rearrangements in each of the lines. Poly(A)+ RNA was extracted from these 7 cell lines, as well as from 6 fresh colon tumors. The mRNA was examined by Northern blot analyses utilizing probes for c-k-ras, c-myc, e-myb, c-fo__~s, c-erb--H, TGFand P53. Together with the Northern analyses, dot blot studies of total RNA from 9 additional fresh tumor tissues demonstrated low levels of expression in both cell lines and fresh tissue using 6 of the probes. However, enhanced c-myc expression was observed in a number of cell lines as well as in fresh tissue. Southern blot analysis revealed amplification of c-myc in 3 of the 7 cell lines. Aberrant expression itself was not associated directly with any chromosome anomalies. Nevertheless, chromosome 7 may prove to be a target towards which future cytogenetie and molecular studies of fresh colon tumors should be directed. The gene c-myc may in turn prove to have some particular significance in colon cancer as it demonstrated the highest levels of expression in both cell lines and fresh tissue. (Supported by PHS grant number CA09299-07, awarded by the NCI, DHHS).
53 *A CYTOGENETIC STUDY OF HUMAN PRIMARY BREAST TUMOR AND NONMALIGANT BREAST TISSUE. Jin S. Lee, Vicki Hopwood, Barbara Tomasovic, Gabriel Hortobagyi, Gary Spitzer, and Sen Pathak. U.T.M.D. Anderson Hospital, 6723 Bertner, Houston, Texas 77030. A cytogenetic study was carried out on 10 primary tumor and 9 nonmalignant breast tissue samples from 11 pts with primary breast cancer after culturing them for 2 wks using the adhesive tumor cell culture system (Cancer Res 46:1263, 1986). Up to 60 metaphase spreads were analyzed after G- or Q-banding. A modal chromosome number was 46. Chromosomes 1,4,5,7,8,12,14,18, and X were frequently involved in numerical or structural alterations. Clonal chromosomal abnormalities were seen in 4 tumor and 3 breast tissue samples. Of these, trisomy 7 was seen in I tumor and breast tissue from the same pt; trisomies 7 and 20 in I tumor; trisomy 8 in I tumor; trisomy 8 a n d t(4;4) in I breast tissue; trisomy 12 in I tumor; inv(1) and t(5;7) in I breast tissue. There was a suggestion of clonal evolution from normal breast tissue to tumor and within breast tumor itself. Further studies are in progress to correlate these cytogenetie data and other biological and clinical variables.
54
* CYTOGENETIC EVOLUTION IN HUMAN OVARIAN CARCINOMA: A SIMPLE METHOD FOR COMPARATIVE ANALYSES. Cynthia G. Roberts and Martin H.N. Tattersal], Ludwig Institute for Cancer Research (Sydney Branch), University of Sydney, Sydney, N.S.W. 2006, AUSTRALIA. Cytogenetic studies of solid tumor tissue are not only confounded by the technical difficulties encountered in their preparation, but also by the high level of karyotypic heterogeneity revealed. This marked heterogeneity results from both the sequential selection of mutant subpopulations involved in tumor progression as well as random changes. Tabular listings of karyotypiu changes provide a wealth of information about the degree of genetic instability of a tumor but are difficult to analyse, especially for comparative studies. One method of analysis is the ordering of identified chromosomal rearrangements according to their observed frequency and relationship to each other. In this way a pattern of clonal evolution may be inferred. Using this method of analysis on a serous ovarian carcinoma from 3 sites in the same patient, we were able to develop a pattern of cytogenetic evolution which may reflect the development of the tumor in vivo. Analysis by this method allows for comparative studies between different metastatic sites whthin the same tumor or of different patients with similar tumor type. Moreover, it may lead to the identification of specific chromosomal changes in tumor development.