Systematic name M376
Brief description The XPRSS-Int network genes down-regulated in breast tumors from patients with germline mutations in BRCA1 [GeneID=672] compared to those with the wild type allele.
Full description or 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17922014   Authors: Pujana MA,Han JD,Starita LM,Stevens KN,Tewari M,Ahn JS,Rennert G,Moreno V,Kirchhoff T,Gold B,Assmann V,Elshamy WM,Rual JF,Levine D,Rozek LS,Gelman RS,Gunsalus KC,Greenberg RA,Sobhian B,Bertin N,Venkatesan K,Ayivi-Guedehoussou N,Solé X,Hernández P,Lázaro C,Nathanson KL,Weber BL,Cusick ME,Hill DE,Offit K,Livingston DM,Gruber SB,Parvin JD,Vidal M
Exact source Table 4S: Difference < 0
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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