Abstract
It has been established that loss of tumour suppressor genes is crucial in carcinogenesis. There has been no reported study on searching for tumour suppressor genes in cholangiocarcinomas as yet. In order to investigate the loss of heterozygosity (LOH), which may represent such gene loss, in cholangiocarcinoma, we studied 14 patients with this tumour using restriction fragment length polymorphism analysis. Twenty-two probes assigned to chromosomes 1, 5, 7, 9, 11, 12, 13, 14, 16, 17 and 18 were used. Allelic losses were found in chromosomal regions 5q35-qter and 17p13. Loss of genetic material in these regions in cholangiocarcinoma was shared with hepatocellular carcinoma. Probes for other chromosomes have as yet shown no consistent LOH. In conclusion, this study for the first time showed LOH on chromosomes 5 and 17 in cholangiocarcinoma.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Armour J. A., Povey S., Jeremiah S., Jeffreys A. J. Systematic cloning of human minisatellites from ordered array charomid libraries. Genomics. 1990 Nov;8(3):501–512. doi: 10.1016/0888-7543(90)90037-u. [DOI] [PubMed] [Google Scholar]
- Armour J. A., Wong Z., Wilson V., Royle N. J., Jeffreys A. J. Sequences flanking the repeat arrays of human minisatellites: association with tandem and dispersed repeat elements. Nucleic Acids Res. 1989 Jul 11;17(13):4925–4935. doi: 10.1093/nar/17.13.4925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ashton-Rickardt P. G., Wyllie A. H., Bird C. C., Dunlop M. G., Steel C. M., Morris R. G., Piris J., Romanowski P., Wood R., White R. MCC, a candidate familial polyposis gene in 5q.21, shows frequent allele loss in colorectal and lung cancer. Oncogene. 1991 Oct;6(10):1881–1886. [PubMed] [Google Scholar]
- Bookstein R., Shew J. Y., Chen P. L., Scully P., Lee W. H. Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science. 1990 Feb 9;247(4943):712–715. doi: 10.1126/science.2300823. [DOI] [PubMed] [Google Scholar]
- Call K. M., Glaser T., Ito C. Y., Buckler A. J., Pelletier J., Haber D. A., Rose E. A., Kral A., Yeger H., Lewis W. H. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. doi: 10.1016/0092-8674(90)90601-a. [DOI] [PubMed] [Google Scholar]
- Cawthon R. M., Weiss R., Xu G. F., Viskochil D., Culver M., Stevens J., Robertson M., Dunn D., Gesteland R., O'Connell P. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990 Jul 13;62(1):193–201. doi: 10.1016/0092-8674(90)90253-b. [DOI] [PubMed] [Google Scholar]
- Czerniak A., Blumgart L. H. Hilar cholangiocarcinoma. Aust N Z J Surg. 1989 Nov;59(11):837–844. doi: 10.1111/j.1445-2197.1989.tb07025.x. [DOI] [PubMed] [Google Scholar]
- Ding S. F., Habib N. A., Dooley J., Wood C., Bowles L., Delhanty J. D. Loss of constitutional heterozygosity on chromosome 5q in hepatocellular carcinoma without cirrhosis. Br J Cancer. 1991 Dec;64(6):1083–1087. doi: 10.1038/bjc.1991.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon E. R., Cho K. R., Nigro J. M., Kern S. E., Simons J. W., Ruppert J. M., Hamilton S. R., Preisinger A. C., Thomas G., Kinzler K. W. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990 Jan 5;247(4938):49–56. doi: 10.1126/science.2294591. [DOI] [PubMed] [Google Scholar]
- Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
- Groden J., Thliveris A., Samowitz W., Carlson M., Gelbert L., Albertsen H., Joslyn G., Stevens J., Spirio L., Robertson M. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. doi: 10.1016/0092-8674(81)90021-0. [DOI] [PubMed] [Google Scholar]
- Higgs D. R., Wainscoat J. S., Flint J., Hill A. V., Thein S. L., Nicholls R. D., Teal H., Ayyub H., Peto T. E., Falusi A. G. Analysis of the human alpha-globin gene cluster reveals a highly informative genetic locus. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5165–5169. doi: 10.1073/pnas.83.14.5165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kinzler K. W., Nilbert M. C., Su L. K., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hedge P., McKechnie D. Identification of FAP locus genes from chromosome 5q21. Science. 1991 Aug 9;253(5020):661–665. doi: 10.1126/science.1651562. [DOI] [PubMed] [Google Scholar]
- Kinzler K. W., Nilbert M. C., Vogelstein B., Bryan T. M., Levy D. B., Smith K. J., Preisinger A. C., Hamilton S. R., Hedge P., Markham A. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991 Mar 15;251(4999):1366–1370. doi: 10.1126/science.1848370. [DOI] [PubMed] [Google Scholar]
- Kondoleon S., Vissing H., Luo X. Y., Magenis R. E., Kellogg J., Litt M. A hypervariable RFLP on chromosome 17p13 is defined by an arbitrary single copy probe p144-D6 [HGM9 No. D17S34]. Nucleic Acids Res. 1987 Dec 23;15(24):10605–10605. doi: 10.1093/nar/15.24.10605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krontiris T. G., DiMartino N. A., Colb M., Parkinson D. R. Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumour DNAs of cancer patients. 1985 Jan 31-Feb 6Nature. 313(6001):369–374. doi: 10.1038/313369a0. [DOI] [PubMed] [Google Scholar]
- Lasko D., Cavenee W., Nordenskjöld M. Loss of constitutional heterozygosity in human cancer. Annu Rev Genet. 1991;25:281–314. doi: 10.1146/annurev.ge.25.120191.001433. [DOI] [PubMed] [Google Scholar]
- Miyaki M., Seki M., Okamoto M., Yamanaka A., Maeda Y., Tanaka K., Kikuchi R., Iwama T., Ikeuchi T., Tonomura A. Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis. Cancer Res. 1990 Nov 15;50(22):7166–7173. [PubMed] [Google Scholar]
- Nakamura Y., Ballard L., Leppert M., O'Connell P., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence (pYNZ22) on chromosome 17p [D17S30]. Nucleic Acids Res. 1988 Jun 24;16(12):5707–5707. doi: 10.1093/nar/16.12.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakamura Y., Fujimoto E., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence pEFD126.3 on chromosome 9q (D9S7). Nucleic Acids Res. 1987 Dec 23;15(24):10607–10607. doi: 10.1093/nar/15.24.10607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakamura Y., Lathrop M., Leppert M., Dobbs M., Wasmuth J., Wolff E., Carlson M., Fujimoto E., Krapcho K., Sears T. Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. Am J Hum Genet. 1988 Nov;43(5):638–644. [PMC free article] [PubMed] [Google Scholar]
- Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sager R. Tumor suppressor genes: the puzzle and the promise. Science. 1989 Dec 15;246(4936):1406–1412. doi: 10.1126/science.2574499. [DOI] [PubMed] [Google Scholar]
- Sell S., Dunsford H. A. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol. 1989 Jun;134(6):1347–1363. [PMC free article] [PubMed] [Google Scholar]
- Storto P. D., Saidman S. L., Demetris A. J., Letessier E., Whiteside T. L., Gollin S. M. Chromosomal breakpoints in cholangiocarcinoma cell lines. Genes Chromosomes Cancer. 1990 Nov;2(4):300–310. doi: 10.1002/gcc.2870020408. [DOI] [PubMed] [Google Scholar]
- Tada M., Omata M., Ohto M. Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing. Cancer Res. 1990 Feb 15;50(4):1121–1124. [PubMed] [Google Scholar]
- Varesco L., Thomas H. J., Cottrell S., Murday V., Fennell S. J., Williams S., Searle S., Sheer D., Bodmer W. F., Frischauf A. M. CpG island clones from a deletion encompassing the gene for adenomatous polyposis coli. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10118–10122. doi: 10.1073/pnas.86.24.10118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Viskochil D., Buchberg A. M., Xu G., Cawthon R. M., Stevens J., Wolff R. K., Culver M., Carey J. C., Copeland N. G., Jenkins N. A. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell. 1990 Jul 13;62(1):187–192. doi: 10.1016/0092-8674(90)90252-a. [DOI] [PubMed] [Google Scholar]
- Voravud N., Foster C. S., Gilbertson J. A., Sikora K., Waxman J. Oncogene expression in cholangiocarcinoma and in normal hepatic development. Hum Pathol. 1989 Dec;20(12):1163–1168. doi: 10.1016/s0046-8177(89)80006-1. [DOI] [PubMed] [Google Scholar]
- Wallace M. R., Marchuk D. A., Andersen L. B., Letcher R., Odeh H. M., Saulino A. M., Fountain J. W., Brereton A., Nicholson J., Mitchell A. L. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science. 1990 Jul 13;249(4965):181–186. doi: 10.1126/science.2134734. [DOI] [PubMed] [Google Scholar]
- Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
- Wong Z., Wilson V., Patel I., Povey S., Jeffreys A. J. Characterization of a panel of highly variable minisatellites cloned from human DNA. Ann Hum Genet. 1987 Oct;51(Pt 4):269–288. doi: 10.1111/j.1469-1809.1987.tb01062.x. [DOI] [PubMed] [Google Scholar]
- vander Straten A., Herzog A., Jacobs P., Cabezón T., Bollen A. Molecular cloning of human haptoglobin cDNA: evidence for a single mRNA coding for alpha 2 and beta chains. EMBO J. 1983;2(6):1003–1007. doi: 10.1002/j.1460-2075.1983.tb01534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]