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117 Chromosome 5 allele loss in familial and sporadic colorectal adenomas
Abstracts 117
19 7 CHROMOSOME 5 ALLELE LOSS IN FAMILIAL AND SPORADIC COLORECTAL ADENOMAS. M. Rees*, S. E. A. Leigh*, J. R. Jasst, A. Gunnl, and J. D. A. Deihanty*. Galton Laboratory, University College London*: Department of Pathology, St. Mark's Hospital London,-; Ashington Hospital, Northumberlandl, U.K.
The characteristics of the autosomal dominant condition, familial adenomatous polyposis, are hyperproliferation of epithelial and mesenchymal tissues [1] and widespread spontaneous chromosome instability [2]. Hundreds of adanomatous polyps are produced in the colon and rectum by the 2nd decade of life; without intervention progression to malignancy is inevitable. The gene for polyposis coli (called APC, adenomatous polyposis coli, in HGM9) has been mapped to chromosome 5q21-22 [3]. According to Knudson's hypothesis inheritance of one mutant form of the gene should be followed by loss or inactivation of the normal allele in tumorigenesis. Loss of chromosomes 5 alleles has been found in 3 of 5 informative APC cancers and in about 20% of sporadic colorectal cancers [4, 5]. However in these previous studies investigation of adenomas from APC patients revealed no loss of restriction fragments from chromosome 5 compared with normal tissue. We wish to report the first examples of such loss in adenomas from polyposis patients and a normal individual. REFERENCES 1. Bussey HJR (1975): Familial Polyposis Coli, Johns Hopkins University Press. 2. Delhanty JDA et al. (1983): Cancer Genet Cytogenet 8:27-50. 3. Bodmer WF et al. (1987): Nature 328:614-616. 4. Okamoto Met al. (1988): Nature 331:273-277. 5. Solomon E et al. (1987): Nature 328:616-619.
118
CYTOGENETIC ANOMALIES OF COLONIC ADENOMA (CA) AS INDICATOR OF MALIGNANT TRANSFORMATION. M.-H. Couturier-Turpin, M. Forest, D. Couturier, C. Esnous, Y. Poirier, and P. Nepveux. Lab. d'Histologie-Biologie cellulaire-cytog6n6tique UER X. Bichat; Groupe de Recherche en Pathologie Digestive, H6pital Cochin, Paris, France.
Anomalies of chromosomes 1, 5,12,17,18 are considered as frequent or even specific in colonic adenocarcinoma (CAK) but their signification is poorly understood. Cytogenetic analysis of CA, which generally precede CAK, might be useful from both a theoretical and practical point of view. The purpose of this study is to precise the cytogenetic anomalies of CA considering 1/those already described in CAK; 2/the risk of malignant transformation of such a tumor. Materials and methods: Chromosomal analysis were done on 8 CA endoscopically resected in 7 patients (M: 5; F: 2) 47 to 82 years old. Within 15 mln following resection small portions of the tip and periphery were submitted for cytogenetic technic as previously described (1). The remaining portion was used for complete histopathologic evaluation. The volume, tissue structure and degree of dysplasia were determined in each tumor; ~nd for each patient, age, history and pathologic associations were considered. Results: Considering the modal number, a main clone can be recognized: pseudodiploid 5/7 CA, hypo (39-42 chr) 1/7, and hyper (52-87 chr) 1/7. Despite a great diversity of cytogenetic aberrations, it has been mainly observed that, the supernumeraries are chromosomes 20 (3/8) and 19 (2/8); chromosome 18 was missing in 80% of the cells in 1/8; in 3 cases, the origins of the rearrangements were determined: #1 inv pterq21; #lp-; #Aq+; #F iso p; in 1 case, dins were present in 25% of the cells. The biggest CA (35 mm in diameter) was hyperdiploid and carried marker #1 and dms. No relationship were observed with degree of dysplasia; the influence of tissue structure could not be determined since all were tubule-villous. It was not suggested relations with the age and associations, CAK or CA(s). Conclusions: analysis of CA showed constant and numerous chromosomal rearrangements: some of them have been observed in CAK and/or in other malignancies. Cytogenetic aberration probably precede changes in tissue phenotype and could represent a more direct indicator of the risk of transformation. [1) Br J Cancer, 46, 856 (1982).
19 7 CHROMOSOME 5 ALLELE LOSS IN FAMILIAL AND SPORADIC COLORECTAL ADENOMAS. M. Rees*, S. E. A. Leigh*, J. R. Jasst, A. Gunnl, and J. D. A. Deihanty*. Galton Laboratory, University College London*: Department of Pathology, St. Mark's Hospital London,-; Ashington Hospital, Northumberlandl, U.K.
The characteristics of the autosomal dominant condition, familial adenomatous polyposis, are hyperproliferation of epithelial and mesenchymal tissues [1] and widespread spontaneous chromosome instability [2]. Hundreds of adanomatous polyps are produced in the colon and rectum by the 2nd decade of life; without intervention progression to malignancy is inevitable. The gene for polyposis coli (called APC, adenomatous polyposis coli, in HGM9) has been mapped to chromosome 5q21-22 [3]. According to Knudson's hypothesis inheritance of one mutant form of the gene should be followed by loss or inactivation of the normal allele in tumorigenesis. Loss of chromosomes 5 alleles has been found in 3 of 5 informative APC cancers and in about 20% of sporadic colorectal cancers [4, 5]. However in these previous studies investigation of adenomas from APC patients revealed no loss of restriction fragments from chromosome 5 compared with normal tissue. We wish to report the first examples of such loss in adenomas from polyposis patients and a normal individual. REFERENCES 1. Bussey HJR (1975): Familial Polyposis Coli, Johns Hopkins University Press. 2. Delhanty JDA et al. (1983): Cancer Genet Cytogenet 8:27-50. 3. Bodmer WF et al. (1987): Nature 328:614-616. 4. Okamoto Met al. (1988): Nature 331:273-277. 5. Solomon E et al. (1987): Nature 328:616-619.
118
CYTOGENETIC ANOMALIES OF COLONIC ADENOMA (CA) AS INDICATOR OF MALIGNANT TRANSFORMATION. M.-H. Couturier-Turpin, M. Forest, D. Couturier, C. Esnous, Y. Poirier, and P. Nepveux. Lab. d'Histologie-Biologie cellulaire-cytog6n6tique UER X. Bichat; Groupe de Recherche en Pathologie Digestive, H6pital Cochin, Paris, France.
Anomalies of chromosomes 1, 5,12,17,18 are considered as frequent or even specific in colonic adenocarcinoma (CAK) but their signification is poorly understood. Cytogenetic analysis of CA, which generally precede CAK, might be useful from both a theoretical and practical point of view. The purpose of this study is to precise the cytogenetic anomalies of CA considering 1/those already described in CAK; 2/the risk of malignant transformation of such a tumor. Materials and methods: Chromosomal analysis were done on 8 CA endoscopically resected in 7 patients (M: 5; F: 2) 47 to 82 years old. Within 15 mln following resection small portions of the tip and periphery were submitted for cytogenetic technic as previously described (1). The remaining portion was used for complete histopathologic evaluation. The volume, tissue structure and degree of dysplasia were determined in each tumor; ~nd for each patient, age, history and pathologic associations were considered. Results: Considering the modal number, a main clone can be recognized: pseudodiploid 5/7 CA, hypo (39-42 chr) 1/7, and hyper (52-87 chr) 1/7. Despite a great diversity of cytogenetic aberrations, it has been mainly observed that, the supernumeraries are chromosomes 20 (3/8) and 19 (2/8); chromosome 18 was missing in 80% of the cells in 1/8; in 3 cases, the origins of the rearrangements were determined: #1 inv pterq21; #lp-; #Aq+; #F iso p; in 1 case, dins were present in 25% of the cells. The biggest CA (35 mm in diameter) was hyperdiploid and carried marker #1 and dms. No relationship were observed with degree of dysplasia; the influence of tissue structure could not be determined since all were tubule-villous. It was not suggested relations with the age and associations, CAK or CA(s). Conclusions: analysis of CA showed constant and numerous chromosomal rearrangements: some of them have been observed in CAK and/or in other malignancies. Cytogenetic aberration probably precede changes in tissue phenotype and could represent a more direct indicator of the risk of transformation. [1) Br J Cancer, 46, 856 (1982).