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Role of loss of heterozygosity on chromosomes 8 and 9 in the development and progression of cancer bladder.
J Egypt Natl Canc Inst. 2005 Dec; 17(4):260-9.JE

Abstract

BACKGROUND

Loss of heterozygosity (LOH) in tumor samples is believed to be a marker for the absence of a functional tumor suppressor gene. Non-random chromosome deletion and LOH at specific chromosomal regions are identified in a number of common human cancers including carcinoma of the bladder, which is considered the most predominant cancer in Egypt due to the prevalence of schistosomiasis.

PURPOSE

The main objective of the present study is to clarify the role of chromosomes 8 and 9 in the establishment and/or progression of schistosomiasis-related bladder cancer through detection of LOH of 8 microsatellite markers on both chromosomes. It also aims to compare the LOH pattern of the tested markers between schistosomiasis- associated and non schistosomiasis-associated bladder cancer.

MATERIAL AND METHODS

To achieve this purpose, DNA was extracted from the tumor specimens and the corresponding peripheral blood samples of 42 primary bladder cancer patients (schistosomal and non schistosomal). Twenty nine of these were diagnosed as squamous cell type (SCC), 11 were transitional (TCC), and 2 were adenocarcinoma (with different stages and grades). LOH at chromosomes 8 and 9 was evaluated for 8 highly polymorphic microsatellite markers distributed at different regions of both chromosomes using the dinucleotide repeat-PCR technique.

RESULTS

The overall percentage of LOH in chromosome 8 was 74% in at least one marker. The highest incidence of LOH was recorded for D8S84 (41%) followed by 37% for D8S87, 29% for D8S85, and 25% for D8S88. Deletions at chromosome 8 were shown to be associated with high grade of the tumor and LOH at D8S85 was associated with metastatic lymph nodes. The overall percentage of LOH in chromosome 9 was 54% and its highest incidence was for D9S126 (36%), followed by 26%, 21%, 19% for D9S166, D9S128 and D9S180, respectively. Fifty nine percent (59%) of the cases with LOH at 9q were diagnosed as squamous cell type (SCC), whereas 9% only were transitional cell type (TCC). No significant association was recorded between the presence of schistosomiasis and LOH detected in all markers used in this study.

CONCLUSION

Our data indicate that more than one tumor suppressor gene on chromosomes 8 and 9 are involved in high grades of bladder carcinogenesis, one at 8p12 and another at 8q21.1 regions. Also, a region at 8q23-quarter may harbor tumor suppressor gene that involved in metastasis of bladder cancer. Our study also revealed that 9p21 (p16INK4) region is involved in both types of the tumor (SCC & TCC). PTCH located at 9q22.3, as well as the TSC gene at 9q34 are involved in squamous cell carcinoma rather than transitional carcinoma. Region 9q12-13 is considered to be a critical region of urothelial tumor suppressor genes. Finally, the present study shows no line of demarcation between schistosomiasis-associate and non schistosomiasis-associated bladder cancer in terms of LOH of the tested microsatellite markers on chromosome 8 and 9. This suggests that data obtained from schistosoma-associated bladder cancer can be extrapolated to bladder cancer induced by a schistosomiasis independent mechanism.

Authors+Show Affiliations

The Department of Biochemistry & Molecular Biology Unit, NCI, Cairo University.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17102820

Citation

Abdel Wahab, Abdel Hady A., et al. "Role of Loss of Heterozygosity On Chromosomes 8 and 9 in the Development and Progression of Cancer Bladder." Journal of the Egyptian National Cancer Institute, vol. 17, no. 4, 2005, pp. 260-9.
Abdel Wahab AH, Abo-Zeid HI, El-Husseini MI, et al. Role of loss of heterozygosity on chromosomes 8 and 9 in the development and progression of cancer bladder. J Egypt Natl Canc Inst. 2005;17(4):260-9.
Abdel Wahab, A. H., Abo-Zeid, H. I., El-Husseini, M. I., Ismail, M., & El-Khor, A. M. (2005). Role of loss of heterozygosity on chromosomes 8 and 9 in the development and progression of cancer bladder. Journal of the Egyptian National Cancer Institute, 17(4), 260-9.
Abdel Wahab AH, et al. Role of Loss of Heterozygosity On Chromosomes 8 and 9 in the Development and Progression of Cancer Bladder. J Egypt Natl Canc Inst. 2005;17(4):260-9. PubMed PMID: 17102820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of loss of heterozygosity on chromosomes 8 and 9 in the development and progression of cancer bladder. AU - Abdel Wahab,Abdel Hady A, AU - Abo-Zeid,Hamdy I, AU - El-Husseini,Motawa I, AU - Ismail,Mohsein, AU - El-Khor,Akmal M, PY - 2006/11/15/pubmed PY - 2007/6/7/medline PY - 2006/11/15/entrez SP - 260 EP - 9 JF - Journal of the Egyptian National Cancer Institute JO - J Egypt Natl Canc Inst VL - 17 IS - 4 N2 - BACKGROUND: Loss of heterozygosity (LOH) in tumor samples is believed to be a marker for the absence of a functional tumor suppressor gene. Non-random chromosome deletion and LOH at specific chromosomal regions are identified in a number of common human cancers including carcinoma of the bladder, which is considered the most predominant cancer in Egypt due to the prevalence of schistosomiasis. PURPOSE: The main objective of the present study is to clarify the role of chromosomes 8 and 9 in the establishment and/or progression of schistosomiasis-related bladder cancer through detection of LOH of 8 microsatellite markers on both chromosomes. It also aims to compare the LOH pattern of the tested markers between schistosomiasis- associated and non schistosomiasis-associated bladder cancer. MATERIAL AND METHODS: To achieve this purpose, DNA was extracted from the tumor specimens and the corresponding peripheral blood samples of 42 primary bladder cancer patients (schistosomal and non schistosomal). Twenty nine of these were diagnosed as squamous cell type (SCC), 11 were transitional (TCC), and 2 were adenocarcinoma (with different stages and grades). LOH at chromosomes 8 and 9 was evaluated for 8 highly polymorphic microsatellite markers distributed at different regions of both chromosomes using the dinucleotide repeat-PCR technique. RESULTS: The overall percentage of LOH in chromosome 8 was 74% in at least one marker. The highest incidence of LOH was recorded for D8S84 (41%) followed by 37% for D8S87, 29% for D8S85, and 25% for D8S88. Deletions at chromosome 8 were shown to be associated with high grade of the tumor and LOH at D8S85 was associated with metastatic lymph nodes. The overall percentage of LOH in chromosome 9 was 54% and its highest incidence was for D9S126 (36%), followed by 26%, 21%, 19% for D9S166, D9S128 and D9S180, respectively. Fifty nine percent (59%) of the cases with LOH at 9q were diagnosed as squamous cell type (SCC), whereas 9% only were transitional cell type (TCC). No significant association was recorded between the presence of schistosomiasis and LOH detected in all markers used in this study. CONCLUSION: Our data indicate that more than one tumor suppressor gene on chromosomes 8 and 9 are involved in high grades of bladder carcinogenesis, one at 8p12 and another at 8q21.1 regions. Also, a region at 8q23-quarter may harbor tumor suppressor gene that involved in metastasis of bladder cancer. Our study also revealed that 9p21 (p16INK4) region is involved in both types of the tumor (SCC & TCC). PTCH located at 9q22.3, as well as the TSC gene at 9q34 are involved in squamous cell carcinoma rather than transitional carcinoma. Region 9q12-13 is considered to be a critical region of urothelial tumor suppressor genes. Finally, the present study shows no line of demarcation between schistosomiasis-associate and non schistosomiasis-associated bladder cancer in terms of LOH of the tested microsatellite markers on chromosome 8 and 9. This suggests that data obtained from schistosoma-associated bladder cancer can be extrapolated to bladder cancer induced by a schistosomiasis independent mechanism. SN - 1110-0362 UR - https://www.unboundmedicine.com/medline/citation/17102820/Role_of_loss_of_heterozygosity_on_chromosomes_8_and_9_in_the_development_and_progression_of_cancer_bladder_ L2 - http://www.nci.cu.edu.eg/Journal/dec2005/CAN_5.pdf DB - PRIME DP - Unbound Medicine ER -