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Network modeling links breast cancer susceptibility and centrosome dysfunction

  1. Author:
    Pujana, M. A.
    Han, J. D. J.
    Starita, L. M.
    Stevens, K. N.
    Tewari, M.
    Ahn, J. S.
    Rennert, G.
    Moreno, V.
    Kirchhoff, T.
    Gold, B.
    Assmann, V.
    ElShamy, W. M.
    Rual, J. F.
    Levine, D.
    Rozek, L. S.
    Gelman, R. S.
    Gunsalus, K. C.
    Greenberg, R. A.
    Sobhian, B.
    Bertin, N.
    Venkatesan, K.
    Ayivi-Guedehoussou, N.
    Sole, X.
    Hernandez, P.
    Lazaro, C.
    Nathanson, K. L.
    Weber, B. L.
    Cusick, M. E.
    Hill, D. E.
    Offit, K.
    Livingston, D. M.
    Gruber, S. B.
    Parvin, J. D.
    Vidal, M.

  2. Author Address

    Harvard Univ, Sch Med, CCSB, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Carmel Hosp, Dept Community Med & Epidemiol, CHS Natl Canc Control Ctr, IL-34362 Haifa, Israel. Technion, Bruce Rappaport Fac Med, IL-34362 Haifa, Israel. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. IDIBELL, Catalan Inst Oncol, Dept Epidemiol, Barcelona 08907, Spain. IDIBELL, Catalan Inst Oncol, Canc Registry, Barcelona 08907, Spain. IDIBELL, Catalan Inst Oncol, Translat Res Lab, Barcelona 08907, Spain. Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. Natl Canc Inst, Human Genet Sect, Lab Genome Divers, Frederick, MD 21702 USA. Univ Hamburg, Hosp Eppendorf, Inst Tumor Biol, Ctr Med Expt, D-20246 Hamburg, Germany. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NYU, Dept Biol, Ctr Comparat Funct Genom, New York, NY 10003 USA. IDIBELL, Catalan Inst Oncol, Translat Res Lab, Barcelona 08907, Spain. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Pujana, MA, Harvard Univ, Sch Med, CCSB, Dept Genet, 44 Binney St, Boston, MA 02115 USA.
    1. Year: 2007
    2. Date: Nov
  2. Journal: Nature Genetics
    1. 39
    2. 11
    3. Pages: 1338-1349
  4. Type of Article: Article
  5. ISSN: 1061-4036
  1. Abstract:

    Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic ( or `omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes.

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External Sources

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  2. DOI: 10.1038/ng.2007.2
  3. View record in Web of Science®
  4. WOS: 000250575900018

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