Biomaterial Database

The molecular basis of breast cancer pathological phenotypes. 2017

Yujing J Heng, and Susan C Lester, and Gary Mk Tse, and Rachel E Factor, and Kimberly H Allison, and Laura C Collins, and Yunn-Yi Chen, and Kristin C Jensen, and Nicole B Johnson, and Jong Cheol Jeong, and Rahi Punjabi, and Sandra J Shin, and Kamaljeet Singh, and Gregor Krings, and David A Eberhard, and Puay Hoon Tan, and Konstanty Korski, and Frederic M Waldman, and David A Gutman, and Melinda Sanders, and Jorge S Reis-Filho, and Sydney R Flanagan, and Deena Ma Gendoo, and Gregory M Chen, and Benjamin Haibe-Kains, and Giovanni Ciriello, and Katherine A Hoadley, and Charles M Perou, and Andrew H Beck

Cancer Research Institute, Beth Israel Deaconess Cancer Center, Boston, MA, USA.

The histopathological evaluation of morphological features in breast tumours provides prognostic information to guide therapy. Adjunct molecular analyses provide further diagnostic, prognostic and predictive information. However, there is limited knowledge of the molecular basis of morphological phenotypes in invasive breast cancer. This study integrated genomic, transcriptomic and protein data to provide a comprehensive molecular profiling of morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases from The Cancer Genome Atlas (TCGA). Morphological features were significantly associated with genomic alteration, DNA methylation subtype, PAM50 and microRNA subtypes, proliferation scores, gene expression and/or reverse-phase protein assay subtype. Marked nuclear pleomorphism, necrosis, inflammation and a high mitotic count were associated with the basal-like subtype, and had a similar molecular basis. Omics-based signatures were constructed to predict morphological features. The association of morphology transcriptome signatures with overall survival in oestrogen receptor (ER)-positive and ER-negative breast cancer was first assessed by use of the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset; signatures that remained prognostic in the METABRIC multivariate analysis were further evaluated in five additional datasets. The transcriptomic signature of poorly differentiated epithelial tubules was prognostic in ER-positive breast cancer. No signature was prognostic in ER-negative breast cancer. This study provided new insights into the molecular basis of breast cancer morphological phenotypes. The integration of morphological with molecular data has the potential to refine breast cancer classification, predict response to therapy, enhance our understanding of breast cancer biology, and improve clinical management. This work is publicly accessible at www.dx.ai/tcga_breast. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

UI	MeSH Term	Description	Entries
D009361	Neoplasm Invasiveness	Ability of neoplasms to infiltrate and actively destroy surrounding tissue.	Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D011960	Receptors, Estrogen	Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.	Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D001943	Breast Neoplasms	Tumors or cancer of the human BREAST.	Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014408	Biomarkers, Tumor	Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or BODY FLUIDS. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including HORMONES; ANTIGENS; amino and NUCLEIC ACIDS; ENZYMES; POLYAMINES; and specific CELL MEMBRANE PROTEINS and LIPIDS.	Biochemical Tumor Marker,Cancer Biomarker,Carcinogen Markers,Markers, Tumor,Metabolite Markers, Neoplasm,Tumor Biomarker,Tumor Marker,Tumor Markers, Biochemical,Tumor Markers, Biological,Biochemical Tumor Markers,Biological Tumor Marker,Biological Tumor Markers,Biomarkers, Cancer,Marker, Biochemical Tumor,Marker, Biologic Tumor,Marker, Biological Tumor,Marker, Neoplasm Metabolite,Marker, Tumor Metabolite,Markers, Biochemical Tumor,Markers, Biological Tumor,Markers, Neoplasm Metabolite,Markers, Tumor Metabolite,Metabolite Markers, Tumor,Neoplasm Metabolite Markers,Tumor Markers, Biologic,Tumor Metabolite Marker,Biologic Tumor Marker,Biologic Tumor Markers,Biomarker, Cancer,Biomarker, Tumor,Cancer Biomarkers,Marker, Tumor,Markers, Biologic Tumor,Markers, Carcinogen,Metabolite Marker, Neoplasm,Metabolite Marker, Tumor,Neoplasm Metabolite Marker,Tumor Biomarkers,Tumor Marker, Biochemical,Tumor Marker, Biologic,Tumor Marker, Biological,Tumor Markers,Tumor Metabolite Markers
D020869	Gene Expression Profiling	The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.	Gene Expression Analysis,Gene Expression Pattern Analysis,Transcript Expression Analysis,Transcriptome Profiling,Transcriptomics,mRNA Differential Display,Gene Expression Monitoring,Transcriptome Analysis,Analyses, Gene Expression,Analyses, Transcript Expression,Analyses, Transcriptome,Analysis, Gene Expression,Analysis, Transcript Expression,Analysis, Transcriptome,Differential Display, mRNA,Differential Displays, mRNA,Expression Analyses, Gene,Expression Analysis, Gene,Gene Expression Analyses,Gene Expression Monitorings,Gene Expression Profilings,Monitoring, Gene Expression,Monitorings, Gene Expression,Profiling, Gene Expression,Profiling, Transcriptome,Profilings, Gene Expression,Profilings, Transcriptome,Transcript Expression Analyses,Transcriptome Analyses,Transcriptome Profilings,mRNA Differential Displays
D023281	Genomics	The systematic study of the complete DNA sequences (GENOME) of organisms. Included is construction of complete genetic, physical, and transcript maps, and the analysis of this structural genomic information on a global scale such as in GENOME WIDE ASSOCIATION STUDIES.	Functional Genomics,Structural Genomics,Comparative Genomics,Genomics, Comparative,Genomics, Functional,Genomics, Structural
D030541	Databases, Genetic	Databases devoted to knowledge about specific genes and gene products.	Genetic Databases,Genetic Sequence Databases,OMIM,Online Mendelian Inheritance In Man,Genetic Data Banks,Genetic Data Bases,Genetic Databanks,Genetic Information Databases,Bank, Genetic Data,Banks, Genetic Data,Data Bank, Genetic,Data Banks, Genetic,Data Base, Genetic,Data Bases, Genetic,Databank, Genetic,Databanks, Genetic,Database, Genetic,Database, Genetic Information,Database, Genetic Sequence,Databases, Genetic Information,Databases, Genetic Sequence,Genetic Data Bank,Genetic Data Base,Genetic Databank,Genetic Database,Genetic Information Database,Genetic Sequence Database,Information Database, Genetic,Information Databases, Genetic,Sequence Database, Genetic,Sequence Databases, Genetic