Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes
| Autor: | Rodney J. Scott, J. Louise Jones, Janet E. Olson, Wei Zheng, Drakoulis Yannoukakos, Fergus J. Couch, Ute Hamann, Carl Blomqvist, Veli-Matti Kosma, Judy Gilbert, Maria Kabisch, Graham G. Giles, Melissa C. Southey, Thomas Rüdiger, Sandra Deming-Halverson, Arto Mannermaa, Jeanette E. Eckel-Passow, Celine M. Vachon, Chen Wang, Vassiliki Kotoula, Angela Cox, Jane Carpenter for Abctc Investigators, George Fountzilas, Simon S. Cross, Päivi Heikkilä, Sotiris Lakis, Kristen S. Purrington, Christine L. Clarke, Diana Eccles, Daniel W. Visscher, Heli Nevanlinna |
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| Přispěvatelé: | Department of Obstetrics and Gynecology, Clinicum, Department of Pathology, Medicum, Department of Oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
0301 basic medicine Cancer Research Pathology medicine.medical_specialty BASAL-LIKE Stromal cell INFILTRATING LYMPHOCYTES SUSCEPTIBILITY LOCI CARCINOMA 3122 Cancers Triple Negative Breast Neoplasms Biology Article OVARIAN-CANCER 03 medical and health sciences 0302 clinical medicine Breast cancer Gene expression Germline mutation medicine Humans Gene Regulatory Networks CANCER PATIENTS LOBULAR INVOLUTION Gene Germ-Line Mutation Aged Regulation of gene expression RISK Tumor microenvironment Tumor biology STROMAL FIBROBLASTS Sequence Analysis RNA Gene Expression Profiling Cancer Middle Aged medicine.disease 3. Good health Gene Expression Regulation Neoplastic Gene expression profiling 030104 developmental biology Oncology 030220 oncology & carcinogenesis T-CELLS Female |
| Popis: | Distinct subtypes of triple negative (TN) breast cancer have been identified by tumor expression profiling. However, little is known about the relationship between histopathologic features of TN tumors, which reflect aspects of both tumor behavior and tumor microenvironment, and molecular TN subtypes. The histopathologic features of TN tumors were assessed by central review and 593 TN tumors were subjected to whole genome expression profiling using the Illumina Whole Genome DASL array. TN molecular subtypes were defined based on gene expression data associated with histopathologic features of TN tumors. Gene expression analysis yielded signatures for four TN subtypes (basal-like, androgen receptor positive, immune, and stromal) consistent with previous studies. Expression analysis also identified genes significantly associated with the 12 histological features of TN tumors. Development of signatures using these markers of histopathological features resulted in six distinct TN subtype signatures, including an additional basal-like and stromal signature. The additional basal-like subtype was distinguished by elevated expression of cell motility and glucose metabolism genes and reduced expression of immune signaling genes, whereas the additional stromal subtype was distinguished by elevated expression of immunomodulatory pathway genes. Histopathologic features that reflect heterogeneity in tumor architecture, cell structure, and tumor microenvironment are related to TN subtype. Accounting for histopathologic features in the development of gene expression signatures, six major subtypes of TN breast cancer were identified. |
| Databáze: | OpenAIRE |
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