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Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer.
Iglesia, Michael D; Vincent, Benjamin G; Parker, Joel S; Hoadley, Katherine A; Carey, Lisa A; Perou, Charles M; Serody, Jonathan S.
Afiliación
  • Iglesia MD; Authors' Affiliations: Lineberger Comprehensive Cancer Center; Curriculum in Genetics and Molecular Biology; Departments of.
  • Vincent BG; Authors' Affiliations: Lineberger Comprehensive Cancer Center; Medicine;
  • Parker JS; Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics;
  • Hoadley KA; Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics;
  • Carey LA; Authors' Affiliations: Lineberger Comprehensive Cancer Center; Medicine;
  • Perou CM; Authors' Affiliations: Lineberger Comprehensive Cancer Center; Genetics; Pathology and Laboratory Medicine; and cperou@med.unc.edu jonathan_serody@med.unc.edu.
  • Serody JS; 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.
Clin Cancer Res ; 20(14): 3818-29, 2014 Jul 15.
Article en En | MEDLINE | ID: mdl-24916698
PURPOSE: 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. EXPERIMENTAL DESIGN: 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. CONCLUSION: 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias de la Mama / Linfocitos B / Neoplasias Basocelulares Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2014 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias de la Mama / Linfocitos B / Neoplasias Basocelulares Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2014 Tipo del documento: Article