© 1995 by Oxford University Press
Journal of the National Cancer Institute, Vol. 87, No. 10, 742-745,
May 17, 1995
© 1995 Oxford University Press
Genetic Alterations at 5p15: a Potential Marker for Progression of Precancerous Lesions of the Uterine Cervix
Memorial sloan-kettering Cancer Center New York, N.Y.
Institute of Cytology and Preventive Oncology, Indian Council of Medical Research New Delhi, India
Memorial Sloan-Kettering Cancer Center
Institute of Cytology and Preventive Oncology, Indian council of Medical Research, Faculty of Medicine Mubarak Al-Kabeer Hospital, Safat
Correspondence to: R. S. K. Chaganti, Ph.D., Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York NY 10021.
Background: Development of uterine cervical cancer is preceded by preneo-plastic proliferative changes in the cervical epithelium called "intra-epithelial neoplasia" or "dysplasia." The genetic basis of the origin and progression of such preneoplastic lesions is not known. By analysis of carcinomas for loss of constitutional heterozygosity (LOH), we have previously shown a high frequency of allelic loss in the short arm of chromosome 5 (5p), suggesting loss of a candidate tumor suppressor gene located in 5p and associated with the development of this tumor. Purpose: To further understand the role of genetic alterations that affect 5p in cervical carcinogenesis, we evaluated the status of microsatellite polymorphisms at five loci mapped to 5pl4-ter in precancerous and cancerous lesions. Methods: Biopsy specimens from two groups of patients were analyzed for genetic alterations affecting 5p. One group comprised 14 cases of precancerous lesions (i.e., dysplasias) and five cases of carcinoma in situ (CIS); the second group comprised 46 previously untreated patients with invasive carcinoma. Tumor and normal DNAs were analyzed by polymerase chain reaction for genetic losses and instability at five polymorphic micro-satellite loci (D5S392, D5S406, D5S208, D5S117, and D5S432) mapped to 5p. Results: LOH was observed in 25 (55.6%) of 45 informative invasive carcinomas, one (20%) of five cases of CIS, and three (21%) of 14 precan-cerous lesions. Among the loci tested, D5S406 (5pl5.1–15.2) exhibited LOH in 12 (48%) of 25 invasive carcinomas, one (33%) of three cases of CIS, and three (60%) of five precancerous lesions, suggesting this to be the site in 5p of the novel candidate tumor suppressor gene. In addition, replication error-type alterations were noted in the 5pl4-ter region in six (13%) of 46 invasive carcinomas, two (40%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Instability affected D5S406 in eight (66.7%) of 12 instances that showed microsatellite instability. Conclusion: These observations suggest that allelic loss and microsatellite instability in the region of D5S406 may play a role early in the development of cervical carcinoma and identify the site of a candidate tumor suppressor gene. These genetic markers (allelic loss and microsatellite instability) may also define CIS and precancerous lesions at high risk for progression to invasive cancer. Implications: The future molecular cloning of the candidate tumor suppressor gene at 5p15.1–15.2 may provide new insights into the genetic mechanisms of cervical carcinogenesis. Analysis and clinical follow-up of a large cohort of prospectively ascertained cases of precancerous lesions would help to validate the usefulness of these markers. [J Natl Cancer Inst 87: 742–745, 1995]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. M. Dong, H.-S. Kim, S.-H. Rha, and D. Sidransky Promoter Hypermethylation of Multiple Genes in Carcinoma of the Uterine Cervix Clin. Cancer Res., July 1, 2001; 7(7): 1982 - 1986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chatterjee, H. A. Pulido, S. Koul, N. Beleño, A. Perilla, H. Posso, M. Manusukhani, and V. V. V. S. Murty Mapping the Sites of Putative Tumor Suppressor Genes at 6p25 and 6p21.3 in Cervical Carcinoma: Occurrence of Allelic Deletions in Precancerous Lesions Cancer Res., March 1, 2001; 61(5): 2119 - 2123. [Abstract] [Full Text]
|
|
|
|
|
|
H. A. Pulido, M. J. Fakruddin, A. Chatterjee, E. D. Esplin, N. Beleño, G. Martínez, H. Posso, G. A. Evans, and V. V. V. S. Murty Identification of a 6-cM Minimal Deletion at 11q23.1-23.2 and Exclusion of PPP2R1B Gene as a Deletion Target in Cervical Cancer Cancer Res., December 1, 2000; 60(23): 6677 - 6682. [Abstract] [Full Text]
|
|
|
|
|
|
Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax Expression in Invasive and in Situ Squamous Cell Carcinoma of the Uterine Cervix Clin. Cancer Res., September 1, 2000; 6(9): 3600 - 3606. [Abstract] [Full Text]
|
|
|
|
|
|
W. M. Lin, E. A. Michalopulos, N. Dhurander, P. C. Cheng, W. Robinson, R. Ashfaq, R. L. Coleman, and C. Y. Muller Allelic Loss and Microsatellite Alterations of Chromosome 3p14.2 Are More Frequent in Recurrent Cervical Dysplasias Clin. Cancer Res., April 1, 2000; 6(4): 1410 - 1414. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Harima, K. Harima, S. Sawada, Y. Tanaka, S. Arita, and T. Ohnishi Loss of Heterozygosity on Chromosome 6p21.2 as a Potential Marker for Recurrence after Radiotherapy of Human Cervical Cancer Clin. Cancer Res., March 1, 2000; 6(3): 1079 - 1085. [Abstract] [Full Text]
|
|