DF/HCC Program Affiliation

Member, Breast Cancer Program

Research Abstract

A major research activity is managing the Brigham and Women’s Hospital breast tumor frozen tissue bank. Since its establishment 4 years ago, the breast tumor bank has become an extensively utilized and invaluable tissue resource to scientists in our affiliated institutions for genomic research, gene validation, somatic mutation screening, and clinical outcomes research. My own research includes gene expression array analysis of human breast tumors to study cancer heterogeneity and taxonomy and to investigate the use of gene expression patterns to predict cancer stage or prognosis. I am particularly interested in the newly described basal-like breast tumor subset identified by expression array analysis. We have performed SNP array-based genome-wide loss-of-heterozygosity (LOH) analysis on the same tumor cohort and have found unique genomic alterations in certain subclasses of breast cancer. Future directions will include further LOH mapping of these unique regions and testing of candidate genes for mutations in the involved tumors. We will also seek to validate expression of specific gene markers for identification of the basal-like tumors by immunohistochemistry on tissue microarrays.

Publications

• Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A 2007 Jun 12; 104(24):10069-74
  PMID: 17537911
• Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007 Mar; 11(3):259-73
  PMID: 17349583
• Maher EA, Brennan C, Wen PY, Durso L, Ligon KL, Richardson A, Khatry D, Feng B, Sinha R, Louis DN, Quackenbush J, Black PM, Chin L, DePinho RA. Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. Cancer Res 2006 Dec 1; 66(23):11502-13
  PMID: 17114236
• Wang ZC, Buraimoh A, Iglehart JD, Richardson 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 2006 Apr 27;
  PMID: 16642273
• Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S. X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 2006 Feb; 9(2):121-32
  PMID: 16473279
• Golshan M, Kuten A, William J, Richardson A, Modarressi A, Matulonis U. Metaplastic carcinoma of the breast with neuroglial differentiation. Breast 2005 Oct 24;
  PMID: 16253505
• Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, Richardson A, Weinberg RA. Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci U S A 2004 Mar 29;
  PMID: 15051869
• Wang ZC, Lin M, Wei LJ, Li C, Miron A, Lodeiro G, Harris L, Ramaswamy S, Tanenbaum DM, Meyerson M, Iglehart JD, Richardson A. Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers. Cancer Res 2004 Jan 1; 64(1):64-71
  PMID: 14729609
• Krop I, Maguire P, Lahti-Domenici J, Lodeiro G, Richardson A, Johannsdottir HK, Nevanlinna H, Borg A, Gelman R, Barkardottir RB, Lindblom A, Polyak K. Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors. Cancer Res 2003 May 1; 63(9):2024-7
  PMID: 12727813
• Signoretti S, Di Marcotullio L, Richardson A, Ramaswamy S, Isaac B, Rue M, Monti F, Loda M, Pagano M. Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer. J Clin Invest 2002 Sep; 110(5):633-41
  PMID: 12208864