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. 1996 Nov;74(10):1578–1585. doi: 10.1038/bjc.1996.592

Mutation of the TP53 gene and allelic imbalance at chromosome 17p13 in ductal carcinoma in situ.

K E Munn 1, R A Walker 1, L Menasce 1, J M Varley 1
PMCID: PMC2074864  PMID: 8932338

Abstract

A panel of 36 cases of preinvasive breast lesions, including 35 cases of ductal carcinoma in situ (DCIS), has been examined for mutation of TP53, allelic imbalance (AI) on 17p13, and expression of TP53, in a number of cases, has been studied using immunohistochemistry. Areas of DCIS, with or without adjacent invasive or benign cells, have been separately microdissected from paraffin-embedded sections and analysed by PCR for genetic changes to chromosome 17p13. TP53 mutations and AI on 17p have been identified in cases of 'pure' DCIS as well as those with associated invasive carcinoma and, furthermore, have been identified in well-differentiated lesions as well as poorly differentiated ones.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen T. I., Gaustad A., Ottestad L., Farrants G. W., Nesland J. M., Tveit K. M., Børresen A. L. Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas. Genes Chromosomes Cancer. 1992 Mar;4(2):113–121. doi: 10.1002/gcc.2870040203. [DOI] [PubMed] [Google Scholar]
  2. Ara S., Lee P. S., Hansen M. F., Saya H. Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res. 1990 Aug 25;18(16):4961–4961. doi: 10.1093/nar/18.16.4961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnes D. M., Bartkova J., Camplejohn R. S., Gullick W. J., Smith P. J., Millis R. R. Overexpression of the c-erbB-2 oncoprotein: why does this occur more frequently in ductal carcinoma in situ than in invasive mammary carcinoma and is this of prognostic significance? Eur J Cancer. 1992;28(2-3):644–648. doi: 10.1016/s0959-8049(05)80117-0. [DOI] [PubMed] [Google Scholar]
  4. Barnes D. M., Hanby A. M., Gillett C. E., Mohammed S., Hodgson S., Bobrow L. G., Leigh I. M., Purkis T., MacGeoch C., Spurr N. K. Abnormal expression of wild type p53 protein in normal cells of a cancer family patient. Lancet. 1992 Aug 1;340(8814):259–263. doi: 10.1016/0140-6736(92)92354-i. [DOI] [PubMed] [Google Scholar]
  5. Betsill W. L., Jr, Rosen P. P., Lieberman P. H., Robbins G. F. Intraductal carcinoma. Long-term follow-up after treatment by biopsy alone. JAMA. 1978 May 5;239(18):1863–1867. doi: 10.1001/jama.239.18.1863. [DOI] [PubMed] [Google Scholar]
  6. Bobrow L. G., Happerfield L. C., Gregory W. M., Millis R. R. Ductal carcinoma in situ: assessment of necrosis and nuclear morphology and their association with biological markers. J Pathol. 1995 Aug;176(4):333–341. doi: 10.1002/path.1711760404. [DOI] [PubMed] [Google Scholar]
  7. Bártek J., Bártková J., Vojtesek B., Stasková Z., Rejthar A., Kovarík J., Lane D. P. Patterns of expression of the p53 tumour suppressor in human breast tissues and tumours in situ and in vitro. Int J Cancer. 1990 Nov 15;46(5):839–844. doi: 10.1002/ijc.2910460515. [DOI] [PubMed] [Google Scholar]
  8. Cornelis R. S., van Vliet M., Vos C. B., Cleton-Jansen A. M., van de Vijver M. J., Peterse J. L., Khan P. M., Børresen A. L., Cornelisse C. J., Devilee P. Evidence for a gene on 17p13.3, distal to TP53, as a target for allele loss in breast tumors without p53 mutations. Cancer Res. 1994 Aug 1;54(15):4200–4206. [PubMed] [Google Scholar]
  9. Davidoff A. M., Kerns B. J., Iglehart J. D., Marks J. R. Maintenance of p53 alterations throughout breast cancer progression. Cancer Res. 1991 May 15;51(10):2605–2610. [PubMed] [Google Scholar]
  10. Don R. H., Cox P. T., Wainwright B. J., Baker K., Mattick J. S. 'Touchdown' PCR to circumvent spurious priming during gene amplification. Nucleic Acids Res. 1991 Jul 25;19(14):4008–4008. doi: 10.1093/nar/19.14.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dupont W. D., Page D. L. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. 1985 Jan 17;312(3):146–151. doi: 10.1056/NEJM198501173120303. [DOI] [PubMed] [Google Scholar]
  12. Eeles R. A., Bartkova J., Lane D. P., Bartek J. The role of TP53 in breast cancer development. Cancer Surv. 1993;18:57–75. [PubMed] [Google Scholar]
  13. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
  14. Futreal P. A., Barrett J. C., Wiseman R. W. An Alu polymorphism intragenic to the TP53 gene. Nucleic Acids Res. 1991 Dec 25;19(24):6977–6977. doi: 10.1093/nar/19.24.6977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gusterson B. A., Machin L. G., Gullick W. J., Gibbs N. M., Powles T. J., Elliott C., Ashley S., Monaghan P., Harrison S. c-erbB-2 expression in benign and malignant breast disease. Br J Cancer. 1988 Oct;58(4):453–457. doi: 10.1038/bjc.1988.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  17. Holland R., Peterse J. L., Millis R. R., Eusebi V., Faverly D., van de Vijver M. J., Zafrani B. Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol. 1994 Aug;11(3):167–180. [PubMed] [Google Scholar]
  18. Jones M. H., Nakamura Y. Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism. Genes Chromosomes Cancer. 1992 Jul;5(1):89–90. doi: 10.1002/gcc.2870050113. [DOI] [PubMed] [Google Scholar]
  19. Lagios M. D., Westdahl P. R., Margolin F. R., Rose M. R. Duct carcinoma in situ. Relationship of extent of noninvasive disease to the frequency of occult invasion, multicentricity, lymph node metastases, and short-term treatment failures. Cancer. 1982 Oct 1;50(7):1309–1314. doi: 10.1002/1097-0142(19821001)50:7<1309::aid-cncr2820500716>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  20. Midgley C. A., Fisher C. J., Bártek J., Vojtesek B., Lane D., Barnes D. M. Analysis of p53 expression in human tumours: an antibody raised against human p53 expressed in Escherichia coli. J Cell Sci. 1992 Jan;101(Pt 1):183–189. doi: 10.1242/jcs.101.1.183. [DOI] [PubMed] [Google Scholar]
  21. Moyret C., Theillet C., Puig P. L., Molés J. P., Thomas G., Hamelin R. Relative efficiency of denaturing gradient gel electrophoresis and single strand conformation polymorphism in the detection of mutations in exons 5 to 8 of the p53 gene. Oncogene. 1994 Jun;9(6):1739–1743. [PubMed] [Google Scholar]
  22. Munn K. E., Walker R. A., Menasce L., Varley J. M. Allelic imbalance in the region of the BRCA1 gene in ductal carcinoma in situ of the breast. Br J Cancer. 1996 Mar;73(5):636–639. doi: 10.1038/bjc.1996.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Munn K. E., Walker R. A., Varley J. M. Frequent alterations of chromosome 1 in ductal carcinoma in situ of the breast. Oncogene. 1995 Apr 20;10(8):1653–1657. [PubMed] [Google Scholar]
  24. Murphy D. S., McHardy P., Coutts J., Mallon E. A., George W. D., Kaye S. B., Brown R., Keith W. N. Interphase cytogenetic analysis of erbB2 and topoII alpha co-amplification in invasive breast cancer and polysomy of chromosome 17 in ductal carcinoma in situ. Int J Cancer. 1995 Feb 20;64(1):18–26. doi: 10.1002/ijc.2910640106. [DOI] [PubMed] [Google Scholar]
  25. Noguchi S., Motomura K., Inaji H., Imaoka S., Koyama H. Clonal analysis of predominantly intraductal carcinoma and precancerous lesions of the breast by means of polymerase chain reaction. Cancer Res. 1994 Apr 1;54(7):1849–1853. [PubMed] [Google Scholar]
  26. O'Malley F. P., Vnencak-Jones C. L., Dupont W. D., Parl F., Manning S., Page D. L. p53 mutations are confined to the comedo type ductal carcinoma in situ of the breast. Immunohistochemical and sequencing data. Lab Invest. 1994 Jul;71(1):67–72. [PubMed] [Google Scholar]
  27. Oliphant A. R., Wright E. C., Swensen J., Gruis N. A., Goldgar D., Skolnick M. H. Dinucleotide repeat polymorphism at the D17S513 locus. Nucleic Acids Res. 1991 Sep 11;19(17):4794–4794. [PMC free article] [PubMed] [Google Scholar]
  28. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  29. Page D. L., Dupont W. D., Rogers L. W., Jensen R. A., Schuyler P. A. Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer. 1995 Oct 1;76(7):1197–1200. doi: 10.1002/1097-0142(19951001)76:7<1197::aid-cncr2820760715>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  30. Page D. L., Dupont W. D., Rogers L. W., Landenberger M. Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer. 1982 Feb 15;49(4):751–758. doi: 10.1002/1097-0142(19820215)49:4<751::aid-cncr2820490426>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  31. Page D. L., Dupont W. D., Rogers L. W., Rados M. S. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer. 1985 Jun 1;55(11):2698–2708. doi: 10.1002/1097-0142(19850601)55:11<2698::aid-cncr2820551127>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  32. Poller D. N., Roberts E. C., Bell J. A., Elston C. W., Blamey R. W., Ellis I. O. p53 protein expression in mammary ductal carcinoma in situ: relationship to immunohistochemical expression of estrogen receptor and c-erbB-2 protein. Hum Pathol. 1993 May;24(5):463–468. doi: 10.1016/0046-8177(93)90157-c. [DOI] [PubMed] [Google Scholar]
  33. Prosser J., Thompson A. M., Cranston G., Evans H. J. Evidence that p53 behaves as a tumour suppressor gene in sporadic breast tumours. Oncogene. 1990 Oct;5(10):1573–1579. [PubMed] [Google Scholar]
  34. Radford D. M., Fair K. L., Phillips N. J., Ritter J. H., Steinbrueck T., Holt M. S., Donis-Keller H. Allelotyping of ductal carcinoma in situ of the breast: deletion of loci on 8p, 13q, 16q, 17p and 17q. Cancer Res. 1995 Aug 1;55(15):3399–3405. [PubMed] [Google Scholar]
  35. Radford D. M., Fair K., Thompson A. M., Ritter J. H., Holt M., Steinbrueck T., Wallace M., Wells S. A., Jr, Donis-Keller H. R. Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast. Cancer Res. 1993 Jul 1;53(13):2947–2949. [PubMed] [Google Scholar]
  36. Rosen P. P., Braun D. W., Jr, Kinne D. E. The clinical significance of pre-invasive breast carcinoma. Cancer. 1980 Aug 15;46(4 Suppl):919–925. doi: 10.1002/1097-0142(19800815)46:4+<919::aid-cncr2820461311>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  37. Sheffield V. C., Beck J. S., Kwitek A. E., Sandstrom D. W., Stone E. M. The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions. Genomics. 1993 May;16(2):325–332. doi: 10.1006/geno.1993.1193. [DOI] [PubMed] [Google Scholar]
  38. Stack M., Jones D., White G., Liscia D. S., Venesio T., Casey G., Crichton D., Varley J., Mitchell E., Heighway J. Detailed mapping and loss of heterozygosity analysis suggests a suppressor locus involved in sporadic breast cancer within a distal region of chromosome band 17p13.3. Hum Mol Genet. 1995 Nov;4(11):2047–2055. doi: 10.1093/hmg/4.11.2047. [DOI] [PubMed] [Google Scholar]
  39. Stratton M. R., Collins N., Lakhani S. R., Sloane J. P. Loss of heterozygosity in ductal carcinoma in situ of the breast. J Pathol. 1995 Feb;175(2):195–201. doi: 10.1002/path.1711750207. [DOI] [PubMed] [Google Scholar]
  40. Tavassoli F. A., Norris H. J. A comparison of the results of long-term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast. Cancer. 1990 Feb 1;65(3):518–529. doi: 10.1002/1097-0142(19900201)65:3<518::aid-cncr2820650324>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  41. Theile M., Hartmann S., Scherthan H., Arnold W., Deppert W., Frege R., Glaab F., Haensch W., Scherneck S. Suppression of tumorigenicity of breast cancer cells by transfer of human chromosome 17 does not require transferred BRCA1 and p53 genes. Oncogene. 1995 Feb 2;10(3):439–447. [PubMed] [Google Scholar]
  42. Thor A. D., Moore DH I. I., Edgerton S. M., Kawasaki E. S., Reihsaus E., Lynch H. T., Marcus J. N., Schwartz L., Chen L. C., Mayall B. H. Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst. 1992 Jun 3;84(11):845–855. doi: 10.1093/jnci/84.11.845. [DOI] [PubMed] [Google Scholar]
  43. Varley J. M., Brammar W. J., Lane D. P., Swallow J. E., Dolan C., Walker R. A. Loss of chromosome 17p13 sequences and mutation of p53 in human breast carcinomas. Oncogene. 1991 Mar;6(3):413–421. [PubMed] [Google Scholar]
  44. Vojtesek B., Bártek J., Midgley C. A., Lane D. P. An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods. 1992 Jul 6;151(1-2):237–244. doi: 10.1016/0022-1759(92)90122-a. [DOI] [PubMed] [Google Scholar]
  45. Walker R. A., Dearing S. J., Lane D. P., Varley J. M. Expression of p53 protein in infiltrating and in-situ breast carcinomas. J Pathol. 1991 Nov;165(3):203–211. doi: 10.1002/path.1711650303. [DOI] [PubMed] [Google Scholar]
  46. Winship P. R. An improved method for directly sequencing PCR amplified material using dimethyl sulphoxide. Nucleic Acids Res. 1989 Feb 11;17(3):1266–1266. doi: 10.1093/nar/17.3.1266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zhuang Z., Merino M. J., Chuaqui R., Liotta L. A., Emmert-Buck M. R. Identical allelic loss on chromosome 11q13 in microdissected in situ and invasive human breast cancer. Cancer Res. 1995 Feb 1;55(3):467–471. [PubMed] [Google Scholar]
  48. van de Vijver M. J., Peterse J. L., Mooi W. J., Wisman P., Lomans J., Dalesio O., Nusse R. Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. N Engl J Med. 1988 Nov 10;319(19):1239–1245. doi: 10.1056/NEJM198811103191902. [DOI] [PubMed] [Google Scholar]

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