title: Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer.
abstract: OBJECTIVE
  Lymphocytic infiltration of tumors predicts improved survival in patients with breast cancer. Previous studies have suggested that this survival benefit is confined predominantly to the basal-like subtype. Immune infiltration in ovarian tumors is also associated with improved prognosis. Currently, it is unclear what aspects of the immune response mediate this improved outcome.
  
  
  METHODS
  Using The Cancer Genome Atlas mRNA-seq data and a large microarray dataset, we evaluated adaptive immune gene expression by genomic subtype in breast and ovarian cancer. To investigate B-cells observed to be prognostic within specific subtypes, we developed methods to analyze B-cell population diversity and degree of somatic hypermutation (SHM) from B-cell receptor (BCR) sequences in mRNA-seq data.
  
  
  RESULTS
  Improved metastasis-free/progression-free survival was correlated with B-cell gene expression signatures, which were restricted mainly to the basal-like and HER2-enriched breast cancer subtypes and the immunoreactive ovarian cancer subtype. Consistent with a restricted epitope-driven response, a subset of basal-like and HER2-enriched breast tumors and immunoreactive ovarian tumors showed high expression of a low-diversity population of BCR gene segments. More BCR segments showed improved prognosis with increased expression in basal-like breast tumors and immunoreactive ovarian tumors compared with other subtypes. Basal-like and HER2-enriched tumors exhibited more BCR sequence variants in regions consistent with SHM.
  
  
  CONCLUSIONS
  Taken together, these data suggest the presence of a productive and potentially restricted antitumor B-cell response in basal-like breast and immunoreactive ovarian cancers. Immunomodulatory therapies that support B-cell responses may be a promising therapeutic approach to targeting these B-cell infiltrated tumors.
authors.affiliation: Authors' Affiliations: Lineberger Comprehensive Cancer Center; Curriculum in Genetics and Molecular Biology; Departments of.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Iglesia
authors.affiliation: Authors' Affiliations: Lineberger Comprehensive Cancer Center; Medicine;
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Vincent
authors.affiliation: Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics;
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics;
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hoadley
authors.affiliation: Authors' Affiliations: Lineberger Comprehensive Cancer Center; Medicine;
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.affiliation: Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics; Pathology and Laboratory Medicine; and cperou@med.unc.edu jonathan_serody@med.unc.edu.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Authors' Affiliations: Lineberger Comprehensive Cancer Center; Medicine; Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina cperou@med.unc.edu jonathan_serody@med.unc.edu.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Serody
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D009154:Mutation; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell