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Loss of heterozygosity, allele silencing and decreased expression of p73 gene in breast cancers: Prevalence of alterations in inflammatory breast cancers

Abstract

The p73 gene is a p53 homologue located at 1p36-33, a region submitted to deletions in breast cancer (BC) and putatively imprinted. To study whether p73 was associated with breast carcinogenesis, loss of heterozygosity (LOH), allele expression and transcript levels were assessed in 59 BC, including 39 BC presenting no inflammatory symptoms (NBC) and 20 inflammatory BC (IBC). IBC is a rare but aggressive form of cancer with a very poor prognosis. Normal breast epithelium (BE) and lymphocytes from patients were used as controls. StyI polymorphism generating GC and/or AT alleles was used to select 22 heterozygous patients. p73 LOH was significantly higher in IBC than in NBC [five of eight cases (62%) versus two of 14 cases (14%); Fisher's exact test, P=0.05]. p73 was biallelically expressed in all BE. In contrast, 12 of 16 (75%) BC were monoallelically expressed, showing that allele silencing was significantly associated with breast carcinogenesis (P=0.012), AT being the preferential silent allele (10 out of 12 tumours). p73 mRNA levels in NBC and IBC were two- and threefold lower than in BE, respectively, suggesting that decreased expression could be related to tumour aggressiveness. In conclusion, LOH, allele silencing and decreased expression of the p73 gene may play a role in breast carcinogenesis.

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References

  • Ahomadegbe JC, Barrois M, Fogel S, LeBihan ML, Douc-Rasy S, Duvillard P, Armand JP and Riou G. . 1995 Oncogene 10: 1217–1227.

  • Beahrs OH, Henson DE, Hutter RVP and Kennedy BJ (eds). . 1992 American Joint Committee on Cancer Manual for Staging of Cancer. Philadelphia: JB Lippincott pp.149–154.

    Google Scholar 

  • Béroud C and Soussi T. . 1998 Nucleic Acids Res. 26: 200–204.

  • Bièche I, Champème MH and Lidereau R. . 1994 Cancer Res. 54: 4274–4276.

  • Cordon-Cardo C and Prives C. . 1999 J. Exp. Med. 190: 1367–1370.

  • De Laurenzi V, Costanzo A, Barcoli D, Terrinoni A, Falco M, Annicchiarico-Petruzzelli M, Levrero M and Melino G. . 1998 J. Exp. Med. 188: 1763–1768.

  • Goyette P, Summer JS, Milos R, Duncan AMV, Rosenblatt DS, Matthews RG and Rozen R. . 1994 Nat. Genet. 7: 195–200.

  • Han S, Semba S, Abe T, Makino N, Furukawa T, Fukushige S, Takahashi HÊ, Sakurada A, Sato M, Shiiba K, Matsumo S, Nimura Y, Nakagawara A and Horii A. . 1999 Eur. J. Surgical Oncol. 25: 194–198.

  • Hudson J, Shoaibi M, Maestro R, Carnero A, Hannon G and Beach DA. . 1999 J. Exp. Med. 190: 1375–1382.

  • Jost CA, Marin MC and Kaelin WG. . 1997 Nature 389: 191–194.

  • Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lellas JM, Dumont X, Ferrara P, Mckeon F and Caput D. . 1997 Cell 90: 809–819.

  • Levine AJ, Momand J and Finlay CA. . 1991 Nature 351: 453–456.

  • Mai M, Yokomizo A, Qian C, Yang P, Tindall DJ, Smith DI and Liu W. . 1998a Cancer Res. 58: 2347–2349.

  • Mai M, Qian C, Yokimizo A, Tindall DJ, Bostwick D, Polychronakos C, Smith DI and Liu W. . 1998b Oncogene 17: 1739–1741.

  • Moll UM, Riou G and Levine AJ. . 1992 Proc. Natl. Acad. Sci. 89: 7262–7266.

  • Peter M, Michon J, Vielh P, Neuenschwander S, Nakamura Y, Sonsino E, Zucker J, Vergnaud G, Thomas G and Delattre O. . 1992 Int. J. Cancer 52: 544–548.

  • Riou G, Lé MG, Travagli JP, Levine AJ and Moll UM. . 1993 J. Natl. Cancer Inst. 85: 1765–1767.

  • Shishikura T, Ichimiya S, Ozaki T, Nimura Y, Kageyama H, Nakamura Y, Sakiyapa S, Miyauchi M, Yamamoto N, Suzuki M, Nakajima N and Nakagawara A. . 1999 Int. J. Cancer (Ped. Oncol.) 84: 321–325.

  • Shittoor SR and Swain S. . 1998 Locally advanced breast cancer: role of medical oncology. In: Bland K, Copeland E (eds). The Breast, Comprehensive Management of Benign and Malignant Diseases, 2nd edn. Vol 2. Saunders: Philadelphia pp.1260–1297.

  • Yang A, Walker N, Bonnet H, Vagner C, Bronson R, Oosterwegel M, Kaghad M, Dikkes P, Sharpe A, McKeon F and Caput D. . 2000 Nature 404: 99–103.

  • Yokomizo A, Mai M, Tindall DJ, Cheng L, Bostwick DG, Naito S, Smith DI and Liu W. . 1999 Oncogene 18: 1629–1633.

  • Zaika AI, Kovalev S, Marchenko ND and Moll UM. . 1999 Cancer Res. 59: 3257–3263.

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Ahomadegbe, J., Tourpin, S., Kaghad, M. et al. Loss of heterozygosity, allele silencing and decreased expression of p73 gene in breast cancers: Prevalence of alterations in inflammatory breast cancers. Oncogene 19, 5413–5418 (2000). https://doi.org/10.1038/sj.onc.1203914

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