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Genome-Wide Analysis for Loss of Heterozygosity in Primary and Recurrent Phyllodes Tumor and Fibroadenoma of Breast using Single Nucleotide Polymorphism Arrays

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Summary

Phyllodes tumors of the breast are biphasic stromal and epithelial tumors histologically similar to benign fibroadenomas, but with a neoplastic stromal component. In contrast to fibroadenoma, phyllodes tumors can recur and be locally aggressive or be malignant. This study uses SNP array analysis to present a genome-wide map of loss of heterozygosity (LOH) in a cohort of phyllodes tumors and fibroadenomas. LOH is frequent and sometimes extensive in phyllodes tumors, but is rarely seen in fibroadenomas. There is heterogeneity between phyllodes tumors of different patients and no one LOH marker identifies a majority of these lesions. However, a subset of LOH loci occur in multiple cases of phyllodes tumors and are not found in fibroadenomas. Primary phyllodes tumors and paired recurrences from the same patient share common regions of LOH. In contrast, metachronous fibroadenomas from the same patient have different LOH patterns with no indication of a shared origin. Specific LOH loci may be associated with pathologic progression in recurrent phyllodes tumors. In a single case of phyllodes tumor containing a malignant epithelial component the malignant epithelium and stroma partially share an LOH genotype, suggesting a common precursor cell for the biphasic malignant components.

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References

  1. Rosen PP (eds): Cystosarcoma Phyllodes (pp. 155–172). Lippincott-Raven Press, New York, 1996

  2. Tavassoli FA(eds): Biphasic Tumors (pp 571–623). Appleton&Langes, Stamford, CT, 1999

  3. Grimes MM, 1992, Cytosarcoma phyllodes of the breast: histologic features, fllow cytometric analysis, and clinical correlations Mod Pathol 5:232–239

    PubMed  CAS  Google Scholar 

  4. Powell CM, Rosen PP, 1994, Adipose differentiation in cytosarcoma phyllodes. A study of 14 cases Am J Surg Pathol 18:720–727

    Article  PubMed  CAS  Google Scholar 

  5. Oberman HA, 1967, Cytosarcoma phyllodes: a clinicopathologic study of hypercellular periductal stroma neoplasms of breast Cancer 18:697–710

    Article  Google Scholar 

  6. Norris HJ, Taylor HB, 1967, Relationship of histologic features to behavior of cystosarcoma phyllodes. Analysis of ninety-four cases Cancer 20:2090–2099

    Article  PubMed  CAS  Google Scholar 

  7. Komenaka IK, El-Tamer M, Pile-Spellman E, Hibshoosh H, 2003, Core needle biopsy as a diagnostic tool to differentiate phyllodes tumor from fibroadenoma Arch Surg 138:987–990

    Article  PubMed  Google Scholar 

  8. Lu YJ, Birdsall S, Osin P, Gusterson B, Shipley J, 1997, Phyllodes tumors of the breast analyzed by comparative genomic hybridization and association of increased 1q copy number with stromal overgrowth and recurrence Genes Chromosomes Cancer 20:275–281

    Article  PubMed  CAS  Google Scholar 

  9. Jee KJ, Gong G, Ahn SH, Park JM, Knuutila S, 2003, Gain in 1q is a common abnormality in phyllodes tumours of the breast Anal Cell Pathol 25:89–93

    PubMed  CAS  Google Scholar 

  10. Ried T, Just KE, Holtgreve-Grez H, du Manoir S, Speicher MR, Schrock E, Latham C, Blegen H, Zetterberg A, Cremer T, Auer G, 1995, Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas Cancer Res 55:5415–5423

    PubMed  CAS  Google Scholar 

  11. Ojopi EP, Rogatto SR, Caldeira JR, Barbieri-Neto J, Squire JA, 2001, Comparative genomic hybridization detects novel amplifications in fibroadenomas of the breast Genes Chromosomes Cancer 30:25–31

    Article  PubMed  CAS  Google Scholar 

  12. Amiel A, Kaufman Z, Goldstein E, Bruchim RB, Kidron D, Gaber E, Fejgin MD, 2003, Application of comparative genomic hybridization in search for genetic aberrations in fibroadenomas of the breast Cancer Genet Cytogenet 142:145–148

    Article  PubMed  CAS  Google Scholar 

  13. Sawyer EJ, Hanby AM, Ellis P, Lakhani SR, Ellis IO, Boyle S, Tomlinson IP, 2000, Molecular analysis of phyllodes tumors reveals distinct changes in the epithelium and stromal components Am J Pathol1093–1098

  14. Kleer CG, Giordano TJ, Braun T, Oberman HA, 2001, Pathologic, immunohistochemical, and molecular features of benign and malignant phyllodes tumors of the breast Mod Pathol 14:185–190

    Article  PubMed  CAS  Google Scholar 

  15. Bot FJ, Sleddens HF, Dinjens WN, 1998, Molecular assessment of clonality leads to the identification of a new germ line TP53 mutation associated with malignant cystosarcoma phyllodes and soft tissue sarcoma Diagn Mol Pathol 7:295–301

    Article  PubMed  CAS  Google Scholar 

  16. Lindblad-Toh K, Tanenbaum DM, Daly MJ, Winchester E, Lui WO, Villapakkam A, Stanton SE, Larsson C, Hudson TJ, Johnson BE, Lander ES, Meyerson M, 2000, Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays Nat Biotechnol 18:1001–1005

    Article  PubMed  CAS  Google Scholar 

  17. Wang ZC, Lin M, Wei LJ, Li C, Miron A, Lodeiro G, Harris L, Ramaswamy S, Tanenbaum DM, Meyerson M, Iglehart JD, Richardson AL, 2004, Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers Cancer Res 64:64–71

    Article  PubMed  CAS  Google Scholar 

  18. McCulloch RK, Sellner LN, Papadimitrou JM, Turbett GR, 1998, The incidence of microsatellite instability and loss of heterozygosity in fibroadenoma of the breast Breast Cancer Res Treat 49:165–169

    Article  PubMed  CAS  Google Scholar 

  19. Li Z, Meng ZH, Sayeed A, Shalaby R, Ljung B-M, Dairkee SH, 2002, Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression Cancer Res 62:5980–5987

    PubMed  CAS  Google Scholar 

  20. Tse GM, Putti TC, Kung FY, Scolyer RA, Law BK, Lau TS, Lee CS, 2002, Increased p53 protein expression in malignant mammary phyllodes tumors Mod Pathol 15:734–743

    Article  PubMed  Google Scholar 

  21. Jagasia AA, Block JA, Qureshi A, Diaz MO, Nobori T, Gitelis S, Lyer AP, 1996, Chromosome 9 related aberrations and deletions of the CDKN2 and MTS2 putative tumor suppressor genes in human chondrosarcomas Cancer Lett 105:91–103

    Article  PubMed  CAS  Google Scholar 

  22. Patrikis MI, Bryan EJ, Thomas NA, Rice GE, Quinn MA, Baker MS, Campbell IG, 2003, Mutation analysis of CDP, TP53, and KRAS in uterine leiomyomas Mol Carcinog 37:61–64

    Article  PubMed  CAS  Google Scholar 

  23. Zeng WR, Scherer SW, Koutsilieris M, Huizenga JJ, Filteau F, Tsui LC, Nepveu A, 1997, Loss of heterozygosity and reduced expression of the CUTL1 gene in uterine leiomyomas Oncogene 14:2355–2365

    Article  PubMed  CAS  Google Scholar 

  24. Roos-Mattjus P, Vroman BT, Burtelow MA, Rauen M, Eapen AK, Karnitz LM, 2002, Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event J Biol Chem 277:43809–43812

    Article  PubMed  CAS  Google Scholar 

  25. Kinzel B, Hall J, Natt F, Weiler J, Cohen D, 2002, Downregulation of Hus1 by antisense oligonucleotides enhances the sensitivity of human lung carcinoma cells to cisplatin Cancer 94:1808–1814

    Article  PubMed  CAS  Google Scholar 

  26. Koh CG, Tan EJ, Manser E, Lim L, 2002, The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family Curr Biol 12:317–321

    Article  PubMed  CAS  Google Scholar 

  27. Harvey BP, Banga SS, Ozer HL, 2004, Regulation of the multifunctional Ca2+/calmodulin dependent protein kinase II by the PP2C phosphatase PPM1F in fibroblasts J Biol Chem 279:24889–24898

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the Harvard SPORE in Breast Cancer (NCI P50 CA89393-01) and by the Breast Cancer Research Foundation. A. Buraimoh was a recipient of an undergraduate research fellowship from the CURE (Continuing Umbrella of Research Experience) program at the Dana-Farber Cancer Institute.

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Correspondence to Andrea Lynn Richardson.

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Wang, Z.C., Buraimoh, A., Iglehart, J.D. et al. Genome-Wide Analysis for Loss of Heterozygosity in Primary and Recurrent Phyllodes Tumor and Fibroadenoma of Breast using Single Nucleotide Polymorphism Arrays. Breast Cancer Res Treat 97, 301–309 (2006). https://doi.org/10.1007/s10549-005-9124-5

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  • DOI: https://doi.org/10.1007/s10549-005-9124-5

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