Skip to main content
SpringerLink
Log in
Book cover

PCR Protocols pp 129–136Cite as

Determination of Loss of Heterozygosity Using Polymerase Chain Reaction

  • Protocol

  • 6386 Accesses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 15))

Abstract

Loss of heterozygosity (LOH) is being detected with increasing frequency in a wide variety of human tumors (1-10). Frequent LOH at a given chromosomal locus implies the existence of a tumor suppressor gene that is important in the pathogenesis of the particular cancer under study. LOH is believed to represent inactivation of one allele of a tumor suppressor gene by chromosomal or subchromosomal deletion. LOH studies have led to the isolation of new tumor suppressor genes (11-13). They have also pinpointed known tumor suppressor genes that may be significant in specific types of cancer (14,15).

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   74.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., Nakamura, Y., White, R., Smits, A. M. M., and Bos, J. L. (1988) Genetic alterations during colorectal-tumor development. N. Engl.. J. Med. 319, 525–532.

    Article  PubMed  CAS  Google Scholar 

  2. Wagata. T., Ishizaki, K., Imamura, M., Shimada, Y., Ikenaga, M., and Tobe, T. (1991) Deletion of 17p and amplification of the int-2 gene in esophageal carcinomas. Cancer Res. 51, 2113–2117.

    PubMed  CAS  Google Scholar 

  3. Meltzer, S. J., Ahnen, D. J., Battifora, H., Yokota, J., and Cline, M. J, (1987) Protooncogene abnormalities in colon cancers and adenomatous polyps. Gastroenterology 92, 1174–1180.

    PubMed  CAS  Google Scholar 

  4. Simon, D., Knowles, B, B., and Weith, A. (1991) Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas. Oncogene 6, 765–770.

    PubMed  CAS  Google Scholar 

  5. Khosla, S., Patel, V. M., Hay, I. D., Schaid, D. J., Grant, C. S., van Heeren, J. U. A., and Thibodeau, S. N. (1991) Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas. J. Clin. Invest. 87, 1691–1699.

    Article  PubMed  CAS  Google Scholar 

  6. Fey, M. F., Hesketh, C., Wainscoat, J. S., Gendler, S., and Thein, S. L. (1989) Clonal allele loss in gastrointestinal cancers. Br. J. Cancer 59, 750–754.

    Article  PubMed  CAS  Google Scholar 

  7. Vogelstein, B., Fearon, E. R., Kern, S. E., Hamilton, S. R., Preisinger, A. C., Nakamura, Y., and White, R. (1989) Allelotype of colorectal carcinomas. Science 244, 207–211.

    Article  PubMed  CAS  Google Scholar 

  8. Kovacs, G., Erlandsson, R., Boldog, F., Ingvarsson, S., Muller-Brechlin, R., Klein, G., and Sumegi, J. (1988) Consistent chromosome 3p deletion and loss of het-erozygosity in renal cell carcinoma. Proc. Natl. Acad. Sci. USA 85, 1571–1575.

    Article  PubMed  CAS  Google Scholar 

  9. Yokota, J., Tsukada, Y., Nakajima, T., Gotoh, M., Shimosato, Y., Mori, N., Tsunokawa, Y., Sugimura, T., and Terada, M. (1989) Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix. Cancer Res. 49, 3598–3601.

    PubMed  CAS  Google Scholar 

  10. Lee, J. H., Kavanagh, J. J., Wildrick, D. M., Wharton, J. T., and Blick, M. (1990) Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. Cancer Res. 50, 2724–2728.

    PubMed  CAS  Google Scholar 

  11. 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., and Vogelstein, B. (1990) Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 247, 49–56.

    Article  PubMed  CAS  Google Scholar 

  12. 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., Carlson, M., Joslyn, G., Groden, J., White, R., Miki, Y., Miyoshi, Y., Nishisho, I., and Nakamura, Y. (1991) Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science 251, 1366–1370.

    Article  PubMed  CAS  Google Scholar 

  13. Kinzler, K. W., Nilbert, M. C., Su, L.-K., Vogelstein, B., Bryan, T. M., Levy, D. B., Smith, K. J., Preisenger, A. C., Hedge, P., McKechnie, D., Finniear, R., Markham, A., Groffen, J., Boguski, M. S., Altschul, S. F., Horii, A., Ando, H., Miyoshi, Y., Miki, Y., Nishosho, I., and Nakamura, Y. (1991) Identification of FAP locus genes from chromosome 5q21. Science 253, 661–665.

    Article  PubMed  CAS  Google Scholar 

  14. Baker, S. J., Fearon, E. R., Nigro, J. M., Hamilton, S. R., Preisinger, A. C., Jessup, J. M., van Tuinen, P., Ledbetter, D. H., Barker, D. F.. Nakamura, Y., White, R., and Vogelstein, B. (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244, 217–221.

    Article  PubMed  CAS  Google Scholar 

  15. Baker, S. J., Preisinger, A. C., Jessup, J. M., Paraskeva, C., Markowitz, S., Willson, J. K. V., Hamilton, S., and Vogelstein, B. (1990) p53 mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res. 50, 7717–7722.

    PubMed  CAS  Google Scholar 

  16. Meltzer, S. J., Mane, S. M., Wood, P. K., Resau, J. H., Newkirk, C., Terzakis, J. A., Korelitz, B. I., Weinstein, W. M., and Needleman, S. W. (1990) Activation of c-Ki-ras in human gastrointestinal dysplasias determined by direct sequencing of polymemse chain reaction products. Cancer Res. 50, 3627–3630.

    PubMed  CAS  Google Scholar 

  17. Reid, B. J., Haggitt, R. C., Rubin, C. E., and Rabinovitch, P. S. (1987) Barrett’s esophagus: Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma. Gastroenterology 93, 1–11.

    PubMed  CAS  Google Scholar 

  18. Meltzer, S. J., Yin, J., Huang, Y., McDaniel, T. K., Newkirk, C., Iseri, O., Vogelstein, B., and Resau, J. H. (1991) Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Proc. Natl. Acad. Sci. USA 88, 4976–4980.

    Article  PubMed  CAS  Google Scholar 

  19. Boynton, R. F., Huang, Y., Blount, P. L., Reid, B. J., Rasking, W. H., Haggitt, R. C., Newkirk, C., Resau, J. H., Yin, J., McDaniel, T., and Meltzer, S. J. (1991) Frequent loss of beterozygosity at tbe retinoblastoma locus in human esophageal cancers. Cancer Res., 51, 5766–5769.

    PubMed  CAS  Google Scholar 

  20. Feinberg, A. P. and Vogelstein, B. (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301, 89–92.

    Article  PubMed  CAS  Google Scholar 

  21. de la Calle-Martin, O., Fabregat, V., Romero, M., Soler, J., Vives, J. and Yague, J. (1990) Acc II polymorphism of the p53 gene. Nucleic Acids Res. 18, 4963.

    Google Scholar 

  22. McGee, T. L., Yandell, D. W., and Dryja, T. P. (1989) Structure and partial genomic sequence of the human retinoblastoma susceptibility gene. Gene 80, 119–128.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Maryland Hospital, Baltimore, MD

    Stephen J. Meltzer

Authors
  1. Stephen J. Meltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Connecticut Health Center, Farmington, CT

    Bruce A. White

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Meltzer, S.J. (1993). Determination of Loss of Heterozygosity Using Polymerase Chain Reaction. In: White, B.A. (eds) PCR Protocols. Methods in Molecular Biology, vol 15. Humana Press, Totowa, NJ. https://doi.org/10.1385/0-89603-244-2:129

Download citation

  • DOI: https://doi.org/10.1385/0-89603-244-2:129

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-0-89603-244-6

  • Online ISBN: 978-1-59259-502-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation