Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes.
Τίτλος | Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Purrington, K. S., Visscher D. W., Wang C., Yannoukakos D., Hamann U., Nevanlinna H., Cox A., Giles G. G., Eckel-Passow J. E., Lakis S., Kotoula V., Fountzilas G., Kabisch M., Rüdiger T., Heikkilä P., Blomqvist C., Cross S. S., Southey M. C., Olson J. E., Gilbert J., Deming-Halverson S., Kosma V-M., Clarke C., Scott R., J Jones L., Zheng W., Mannermaa A., Eccles D. M., Vachon C. M., & Couch F. J. |
Corporate Authors | Jane Carpenter for ABCTC Investigators |
Journal | Breast Cancer Res Treat |
Volume | 157 |
Issue | 1 |
Pagination | 117-31 |
Date Published | 2016 05 |
ISSN | 1573-7217 |
Λέξεις κλειδιά | Adult, Aged, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Germ-Line Mutation, Humans, Middle Aged, Sequence Analysis, RNA, Triple Negative Breast Neoplasms |
Abstract | 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. |
DOI | 10.1007/s10549-016-3775-2 |
Alternate Journal | Breast Cancer Res. Treat. |
PubMed ID | 27083182 |
PubMed Central ID | PMC5400013 |
Grant List | R25 CA092049 / CA / NCI NIH HHS / United States R01 CA100374 / CA / NCI NIH HHS / United States U01 CA116167 / CA / NCI NIH HHS / United States R01 CA116167 / CA / NCI NIH HHS / United States P50 CA116201 / CA / NCI NIH HHS / United States R01 CA192393 / CA / NCI NIH HHS / United States |