Identification of p53 Gene Mutations in Bladder Cancers and Urine Samples

American Association for the Advancement of Science (AAAS) - Tập 252 Số 5006 - Trang 706-709 - 1991
David Sidransky1, Andrew von Eschenbach2, Yvonne Tsai3, Peter A. Jones3, Ian C. Summerhayes4, Fray F. Marshall5, Meera Paul1, Pearl Green6, Stanley R. Hamilton6, Philip Frost7, Bert Vogelstein1
1Department of Oncology, Johns Hopkins University, Baltimore, MD 21231.
2Department of Urology, M. D. Anderson Hospital Houston, TX 77054.
3Kenneth J. Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033.
4Department of Surgery, Harvard Medical School, Boston, MA 02115.
5Department of Urology, Johns Hopkins University, Baltimore, MD 21215.
6Department of Pathology, Johns Hopkins University, Baltimore, MD 21231
7Department of Cell Biology, M. D. Anderson Hospital Houston, TX 77054.

Tóm tắt

Although bladder cancers are very common, little is known about their molecular pathogenesis. In this study, invasive bladder cancers were evaluated for the presence of gene mutations in the p53 suppressor gene. Of 18 tumors evaluated, 11 (61 percent) were found to have genetic alterations of p53. The alterations included ten point mutations resulting in single amino acid substitutions, and one 24-base pair deletion. In all but one case, the mutations were associated with chromosome 17p allelic deletions, leaving the cells with only mutant forms of the p53 gene product. Through the use of the polymerase chain reaction and oligomer-specific hybridization, p53 mutations were identified in 1 to 7 percent of the cells within the urine sediment of each of three patients tested. The p53 mutations are the first genetic alterations demonstrated to occur in a high proportion of primary invasive bladder cancers. Detection of such mutations ex vivo has clinical implications for monitoring individuals whose tumor cells are shed extracorporeally.

Từ khóa


Tài liệu tham khảo

ATKIN, N.B., CYTOGENETIC STUDY OF 10 CARCINOMAS OF THE BLADDER - INVOLVEMENT OF CHROMOSOME-1 AND CHROMOSOME-11, CANCER GENETICS AND CYTOGENETICS 15: 253 (1985).

BADALAMENT, R.A., SEMIN UROL 6: 22 (1988).

Baker S. J. Nuclear Processes and Oncogenes (1992).

10.1126/science.2649981

10.1126/science.2144057

BARTEK, J, GENETIC AND IMMUNOCHEMICAL ANALYSIS OF MUTANT P53 IN HUMAN BREAST-CANCER CELL-LINES, ONCOGENE 5: 893 (1990).

CHENG, J, FREQUENT MUTATIONS IN THE P53 TUMOR SUPPRESSOR GENE IN HUMAN LEUKEMIA T-CELL LINES, MOLECULAR AND CELLULAR BIOLOGY 10: 5502 (1990).

COON J COMMUNICATION.

DEITCH, A.D., A CLINICALLY APPLICABLE METHOD TO PRESERVE URINE AND BLADDER WASHING CELLS FOR FLOW CYTOMETRIC MONITORING OF BLADDER-CANCER PATIENTS, JOURNAL OF UROLOGY 143: 700 (1990).

10.1073/pnas.76.5.2420

DELSENNO, L, DIFFERENTIAL HYPOMETHYLATION OF THE C-MYC PROTOONCOGENE IN BLADDER CANCERS AT DIFFERENT STAGES AND GRADES, JOURNAL OF UROLOGY 142: 146 (1989).

DILLER, L, P53 FUNCTIONS AS A CELL-CYCLE CONTROL PROTEIN IN OSTEOSARCOMAS, MOLECULAR AND CELLULAR BIOLOGY 10: 5772 (1990).

10.1038/312646a0

ELIYAHU, D, METH-A FIBRO-SARCOMA CELLS EXPRESS 2 TRANSFORMING MUTANT P53 SPECIES, ONCOGENE 3: 313 (1988).

10.1073/pnas.86.22.8763

10.1038/318377a0

10.1126/science.6304875

10.1016/0092-8674(89)90045-7

FOOT, N.C., CANCER (BRUSSELS) 11: 127 (1958).

FUJITA, J, FREQUENCY OF MOLECULAR ALTERATIONS AFFECTING RAS PROTOONCOGENES IN HUMAN URINARY-TRACT TUMORS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 82: 3849 (1985).

GIBAS, Z, NONRANDOM CHROMOSOMAL CHANGES IN TRANSITIONAL CELL-CARCINOMA OF THE BLADDER, CANCER RESEARCH 44: 1257 (1984).

HANSEN, M.F., GENETICS OF CANCER PREDISPOSITION, CANCER RESEARCH 47: 5518 (1987).

10.1128/jvi.63.2.739-746.1989

10.1073/pnas.87.7.2775

10.1016/0140-6736(90)90801-B

10.1038/312651a0

KEOHAVONG, P, FIDELITY OF DNA-POLYMERASES IN DNA AMPLIFICATION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 86: 9253 (1989).

KNUDSON, A.G., HEREDITARY CANCER, ONCOGENES, AND ANTIONCOGENES, CANCER RESEARCH 45: 1437 (1985).

KOGAN, S.C., AN IMPROVED METHOD FOR PRENATAL-DIAGNOSIS OF GENETIC-DISEASES BY ANALYSIS OF AMPLIFIED DNA-SEQUENCES - APPLICATION TO HEMOPHILIA-A, NEW ENGLAND JOURNAL OF MEDICINE 317: 985 (1987).

KOSS, L.G., DIAGNOSTIC-VALUE OF CYTOLOGY OF VOIDED URINE, ACTA CYTOLOGICA 29: 810 (1985).

Koss L. G. Diagnostic Cytology and Its Histopathologic Bases (1979).

KRAFT, R, USING MINI-PREP PLASMID DNA FOR SEQUENCING DOUBLE-STRANDED TEMPLATES WITH SEQUENASE, BIOTECHNIQUES 6: 544 (1988).

10.1128/jvi.62.12.4737-4744.1988

10.1038/278261a0

10.1016/0092-8674(79)90293-9

MASKUS, J.R., UROLOGICAL RESEARCH 6: 341 (1988).

10.1073/pnas.87.14.5435

MERCER, W.F., JOURNAL OF CELLULAR BIOCHEMISTRY 44 14C: 285 (1990).

MUNROE, D.G., LOSS OF A HIGHLY CONSERVED DOMAIN ON P53 AS A RESULT OF GENE DELETION DURING FRIEND VIRUS-INDUCED ERYTHROLEUKEMIA, ONCOGENE 2: 621 (1988).

NAKAZAWA, H, RELATIONSHIP BETWEEN CHEMICALLY-INDUCED HA-RAS MUTATION AND TRANSFORMATION OF BALB/C 3T3 CELLS - EVIDENCE FOR CHEMICAL-SPECIFIC ACTIVATION AND CELL TYPE SPECIFIC RECRUITMENT OF ONCOGENE IN TRANSFORMATION, MOLECULAR CARCINOGENESIS 3: 202 (1990).

NEAL, D.E., EPIDERMAL-GROWTH-FACTOR RECEPTORS IN HUMAN BLADDER-CANCER - COMPARISON OF INVASIVE AND SUPERFICIAL TUMORS, LANCET 1: 366 (1985).

10.1038/342705a0

10.1038/312649a0

RAGHAVAN, D, BIOLOGY AND MANAGEMENT OF BLADDER-CANCER, NEW ENGLAND JOURNAL OF MEDICINE 322: 1129 (1990).

REDDY, E.P., A POINT MUTATION IS RESPONSIBLE FOR THE ACQUISITION OF TRANSFORMING PROPERTIES BY THE T24 HUMAN BLADDER-CARCINOMA ONCOGENE, NATURE 300: 149 (1982).

10.1073/pnas.87.19.7555

SIDRANSKY D unpublished data.

Speissl B. TNM-Atlas: Illustrated Guide to the Classification of Malignant Tumors (1982).

STANBRIDGE, E.J., HUMAN TUMOR SUPPRESSOR GENES, ANNUAL REVIEW OF GENETICS 24: 615 (1990).

TABIN, C.J., MECHANISM OF ACTIVATION OF A HUMAN ONCOGENE, NATURE 300: 143 (1982).

10.1126/science.2554494

TSAI, Y.C., CANCER RESEARCH 50: 44 (1990).

VOGELSTEIN, B, RAPID PURIFICATION OF DNA FROM AGAROSE GELS BY CENTRIFUGATION THROUGH A DISPOSABLE PLASTIC COLUMN, ANALYTICAL BIOCHEMISTRY 160: 115 (1987).

WEINBERG, R.A., ONCOGENES, ANTIONCOGENES, AND THE MOLECULAR-BASES OF MULTISTEP CARCINOGENESIS, CANCER RESEARCH 49: 3713 (1989).

Thông tin
Thông tin xuất bản

American Association for the Advancement of Science (AAAS)

Tập 252 Số 5006

706-709

Thông tin tác giả