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Clinicopathological characteristics of breast carcinomas with allelic loss in the p73

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Abstract

p73, a new member of the p53 family, has been mapped to chromosome 1p 36, a region where loss of heterozygosity (LOH) is frequently observed in primary human tumors. Allelic loss studies involving the 1p arm in breast carcinomas offer rates ranging from 13% to 75%, depending on the genetic interval being studied. We investigated LOH in an intragenic microsatellite marker, and those centromerically flanking the p73 gene, at 1p 36, and their correlations with patient age and 10 pathologic parameters in a series of 193 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using five markers of the 1p 36 region (p73P1, D1S2694, D1S214, D1S2666 and D1S450). LOH was found in at least one of these markers in 27% of tumors. When we established the comparison between tumors with and without LOH and the distribution of the 10 pathologic parameters considered, we observed statistically significant differences in association with higher histologic grade (p = 0.02), more advanced pathological stage (p = 0.02), peritumoral vessel involvement (p = 0.04) and poorly differentiated carcinomas (p = 0.01), as well as in tumors that concomitantly exhibited lymph node metastases, peritumoral vessel involvement and absence of steroid receptors (p = 0.02). These data suggest that LOH in the p73 region could be pathogenically related to breast cancer and possibly to a poor tumor prognosis.

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References

  1. Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D: Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90: 809-819, 1997

    Google Scholar 

  2. Schwab M, Praml C, Amler LC: Genomic instability in 1p and human malignancies. Genes Chrom Cancer 16: 211-229, 1996

    Google Scholar 

  3. Yang A, Kaghad M, Wang Y, Gillet E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F: p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2: 305-316, 1998

    Google Scholar 

  4. Nomoto S, Haruki N, Kondo M, Konishi H, Takahashi T, Takahashi T: Search for mutations and examination of allelic expression imbalance of the p73 gene at 1p36.3 in human lung cancers. Cancer Res 58: 1380-1383, 1998

    Google Scholar 

  5. Tsao H, Zhang X, Majewski P, Haluska FG: Mutational and expression analysis of the p73 gene in melanoma cell lines. Cancer Res 59: 172-174, 1999

    Google Scholar 

  6. Ichimiya S, Nimura Y, Kageyama H, Takada N, Sunahara M, Shishikura T, Nakamura Y, Sakiyama S, Seki N, Ohira M, Kaneko Y, McKeon F, Caput D, Nakagawara A: p73 at chromosome 1p36.3 is lost in advanced stage neuroblastoma but its mutation is infrequent. Oncogene 18: 1061-1066, 1999

    Google Scholar 

  7. Zaika AI, Kovalev S, Marchenko ND, Moll UM: Overexpression of the wild type p73 gene in breast cancer tissues and cell lines. Cancer Res 59: 3257-3263, 1999

    Google Scholar 

  8. Di Como CJ, Gaiddon C, Prives C: p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol Cell Biol 19: 1438-1449, 1999

    Google Scholar 

  9. Jost CA, Marin MC, Kaelin WG: p73 is a human p53-related protein that can induce apoptosis. Nature 389: 191-194, 1997

    Google Scholar 

  10. Kovalev S, Marchenko N, Swendeman S, LaQuaglia M, Moll UM: Expression level, allelic origin, and mutation analysis of the p73 gene in neuroblastoma tumors and cell lines. Cell Growth Differ 9: 897-903, 1998

    Google Scholar 

  11. Chi SG, Chang SG, Lee SJ, Lee CH, Kim JI, Park JH: Elevated and biallelic expression of p73 is associated with progression of human bladder cancer. Cancer Res 59: 2791-2793, 1999

    Google Scholar 

  12. Mai M, Yokomizo A, Qian C, Yang P, Tindall DJ, Smith DI, Liu W: Activation of p73 silent allele in lung cancer. Cancer Res 58: 2347-2349, 1998

    Google Scholar 

  13. Han S, Semba S, Abe T, Makino N, Furukawa T, Fukushige S, Takahashi H, Sakurada A, Sato M, Shiiba K, Matsuno S, Nimura Y, Nakagawara A, Horii A: Infrequent somatic mutations of the p73 gene in various human cancers. Eur J Surg Oncol 25: 194-198, 1999

    Google Scholar 

  14. Shishikura T, Ichimiya S, Ozaki T, Nimura Y, Kageyama H, Nakamura Y, Sakiyama S, Miyauchi M; Yamamoto N, Suzuki M, Nakajima N, Nakagawara A: Mutational analysis of the p73 gene in human breast cancers. Int J Cancer 84: 321-325, 1999

    Google Scholar 

  15. Harada Y, Katagiri T, Ito I, Akiyama F, Sakamoto G, Kasumi F, Nakamura Y, Emi M: Genetic studies of 457 breast cancers: Clinicopathologic parameters compared with genetic alterations. Cancer 74: 2281-2286, 1994

    Google Scholar 

  16. Genuardi M, Tsihira H, Anderson DE, Saunders GF: Distal deletion of chromosome 1p in ductal carcinoma of the breast. Am J Hum Genet 45: 73-82, 1989

    Google Scholar 

  17. Borg A, Zhang QX, Olsson H, Wenngren E: Chromosome 1 alterations in breast cancer: allelic loss on 1p and 1q is related to lymphogenic metastases and poor prognosis. Genes Chrom Cancer 5: 311-320, 1992

    Google Scholar 

  18. Nagai H, Negrini M, Carter SL, Gillum DR, Rosenberg AL, Schwartz GF, Croce CM: Detection and cloning of a common region of loss of heterozygosity at chromosome 1p in breast cancer. Cancer Res 55: 1752-1757, 1995

    Google Scholar 

  19. Farabegoli F, Ceccarelli C, Santini D, Trere D, Baldini N, Taffurelli M, Derenzini M: Chromosome 1 aneusomy with 1p36 under-representation is related to histologic grade, DNA aneuploidy, high c-erb B-2 and loss of bcl-2 expression in ductal breast carcinoma. Int J Cancer 69: 381-385, 1996

    Google Scholar 

  20. Tsukamoto K, Ito N, Yoshimoto M, Kasumi F, Akiyama F, Sakamoto G, Nakamura Y, Emi M: Allelic loss on chromosome 1p is associated with progression and lymph node metastasis of primary breast carcinoma. Cancer 82: 317-322, 1998

    Google Scholar 

  21. Millikan RC, Ingles SA, Diep AT, Xue S, Zhou N, Florentine BD, Sparkes RS, Haile RW: Linkage analysis and loss of heterozygosity for chromosome arm 1p in familial breast cancer. Genes Chrom Cancer 25: 354-361, 1999

    Google Scholar 

  22. Bieche I, Khodja A, Lidereau R: Deletion mapping of chromosomal region 1p32-pter in primary breast cancer. Genes Chrom Cancer 24: 255-263, 1999

    Google Scholar 

  23. Ragnarsson G, Eiriksdottir G, Johannsdottir JT, Jonasson JG, Egilsson V, Ingvarsson S: Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival. Br J Cancer 79: 1468-1474, 1999

    Google Scholar 

  24. Nimura Y, Mihara M, Ichimiya S, Sakiyama S, Seki N, Ohira M, Nomura N, Fujimori M, Adachi W, Amano J, He M, Ping Y-M, Nakagawara A: p73, a gene related to p53, is not mutated in esophageal carcinomas. Int J Cancer 78: 437-440, 1998

    Google Scholar 

  25. Oto M, Miyake S, Yuasa Y: Optimization of nonradioisotopic single strand conformation polymorphism analysis with a conventional minislab gel electrophoresis apparatus. Ann Biochem 213: 19-22, 1993

    Google Scholar 

  26. Sunahara M, Ichimiya S, Nimura Y, Takada N, Sakiyama S, Sato Y, Todo S, Adachi W, Amano J, Nakagawara A: Mutational analysis of the p73 gene localized at chromosome 1p36.3 in colorectal carcinomas. Int J Oncol 13: 319-323, 1998

    Google Scholar 

  27. Corn PG, Kuerbitz SJ, van Noesel MM, Esteller M, Compitello N, Baylin SB, Herman JG: Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 50 Cpg island methylation. Cancer Res 59: 3352-3356, 1999

    Google Scholar 

  28. Kawano S, Miller CW, Gombart AF, Bartram CR, Matsuo Y, Asou H, Sakashita A, Said J, Tatsumi E, Koeffler HP: Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation. Blood 94: 1113-1120, 1999

    Google Scholar 

  29. Devilee P, Cornelisse C: Somatic genetic changes in human breast cancer. Biochim Biophys Acta 1198: 113-130, 1994

    Google Scholar 

  30. Biéche I, Lidereau R: Genetic alterations in breast cancer. Genes Chrom Cancer 14: 227-251, 1995

    Google Scholar 

  31. Kerangueven F, Noguchi T, Coulier F, Allione F, Wargniez V, Simony-Lafontaine J, Longy M, Jackemier J, Sobol H, Eisinger F, Birnbaum D: Genome-wide search for loss of heterozygosity shows extensive genetic diversity of human breast carcinomas. Cancer Res 57: 5469-5474, 1997

    Google Scholar 

  32. Phelan CM, Borg A, Cuny M, Crichton DN, Baldersson T, Andersen TI, Caligo MA, Lidereau R, Lidblom A, Seitz S, Kelsell D, Hamann U, Rio P, Thorlacious S, Papp J, Olah E, Ponder B, Bignon YJ, Scherneck S, Barkardottir R, Borresen-Dale AL, Eyfjörd J, Theillet C, Thompson AM, Devilee P, Larsson C: Consortium study on 1280 breast carcinomas: Allelic loss on chromosome 17 targets subregions associated with family history and clinical parameters. Cancer Res 58: 1004-1012, 1998

    Google Scholar 

  33. Harris JR, Morrow M, Norton L: Malignant tumors of the breast. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer Principles and Practice of Oncology. 5th Edtion, Vol 2, Lippincott-Noreu, Philadelphia, 1997, pp 1557-1616

    Google Scholar 

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Dominguez, G., Silva, J., Silva, J.M. et al. Clinicopathological characteristics of breast carcinomas with allelic loss in the p73. Breast Cancer Res Treat 63, 17–22 (2000). https://doi.org/10.1023/A:1006446709715

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