microrna-amplification-recognition-through-locked-nucleic-acid-situ

MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as a Novel Detection and Quantification Method

When using traditional probe-based in situ hybridization (ISH) imaging detection methods, microRNAs (miRNAs) are difficult to capture due to their size, ...

rna-situ-hybridization-with-sequential-protein-immunofluorescence

RNA In situ Hybridization with Sequential Protein Immunofluorescence in Tandem Assay

The functionality of cells within a host does not depend on isolated signals. Instead, all components, from the smallest RNA molecules to the largest ...

sequential-detection-biomolecules-formalin-fixed-paraffin-embedded

Sequential Detection of Biomolecules in Formalin-fixed, Paraffin-embedded Samples with Mass Spectrometry Imaging

Tissues are complex cellular environments, made up of a vast array of cell types and biomolecules all interacting with each other to carry out the ...

comprehensive-spatial-profiling-species-agnostic-transcriptomes-via

Comprehensive Spatial Profiling of Species-agnostic Transcriptomes via Stereo-seq

The spatial composition of cells within the host, as well as the bacteria or viral loads within the tissue, can impact the interaction of cell types and ...

dual-modality-molecular-cartography-integrating-multiplex-mrna

Dual-modality Molecular Cartography: Integrating Multiplex mRNA Detection with Protein Imaging Mass Cytometry

The ability to detect protein and mRNA in the same assay helps us understand how the cell is priming for an arrival and what cues it receives as it ...

The University of Texas MD Anderson Cancer Center

Ductal carcinoma in situ (DCIS) is the most frequently diagnosed early-stage breast cancer. Only a subset of patients progress to invasive ductal carcinoma (IDC), and this presents a formidable clinical challenge for determining which patients to treat aggressively and which patients to monitor without therapeutic intervention. Understanding the molecular and genomic basis of invasion has been difficult to study in DCIS cancers due to several technical obstacles, including low tumour cellularity, lack of fresh-frozen tissues, and intratumour heterogeneity. In this review, we discuss the role of intratumour heterogeneity in the progression of DCIS to IDC in the context of three evolutionary models: independent lineages, evolutionary bottlenecks, and multiclonal invasion. We examine the evidence in support of these models and their relevance to the diagnosis and treatment of patients with DCIS. We also discuss how emerging technologies, such as single-cell sequencing, STAR-FISH, and imaging mass spectrometry, are likely to provide new insights into the evolution of this enigmatic disease. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Genome evolution in ductal carcinoma in situ: invasion of the clones.

Ductal carcinoma in situ (DCIS) is an early-stage breast cancer that infrequently progresses to invasive ductal carcinoma (IDC). Genomic evolution has been difficult to delineate during invasion due to intratumor heterogeneity and the low number of tumor cells in the ducts. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS) to measure genomic copy number profiles of single tumor cells while preserving their spatial context in tissue sections. We applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions in addition to exome sequencing. Our data reveal a direct genomic lineage between in situ and invasive tumor subpopulations and further show that most mutations and copy number aberrations evolved within the ducts prior to invasion. These results support a multiclonal invasion model, in which one or more clones escape the ducts and migrate into the adjacent tissues to establish the invasive carcinomas.

Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing.

Ductal carcinoma in situ (DCIS) is the most common form of preinvasive breast cancer and, despite treatment, a small fraction (5-10%) of DCIS patients develop subsequent invasive disease. A fundamental biologic question is whether the invasive disease arises from tumor cells in the initial DCIS or represents new unrelated disease. To address this question, we performed genomic analyses on the initial DCIS lesion and paired invasive recurrent tumors in 95 patients together with single-cell DNA sequencing in a subset of cases. Our data show that in 75% of cases the invasive recurrence was clonally related to the initial DCIS, suggesting that tumor cells were not eliminated during the initial treatment. Surprisingly, however, 18% were clonally unrelated to the DCIS, representing new independent lineages and 7% of cases were ambiguous. This knowledge is essential for accurate risk evaluation of DCIS, treatment de-escalation strategies and the identification of predictive biomarkers.

Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer.

Principal component analysis (PCA), a standard approach to analysis and visualization of large datasets, is commonly used in biomedical research for detecting similarities and differences among groups of samples. We initially used conventional PCA as a tool for critical quality control of batch and trend effects in multi-omic profiling data produced by The Cancer Genome Atlas (TCGA) project of the NCI. We found, however, that conventional PCA visualizations were often hard to interpret when inter-batch differences were moderate in comparison with intra-batch differences; it was also difficult to quantify batch effects objectively. We, therefore, sought enhancements to make the method more informative in those and analogous settings.

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Article	Year
Genome evolution in ductal carcinoma in situ: invasion of the clones. The Journal of pathology\| PubMed ID: 27861897	2017
Multiclonal Invasion in Breast Tumors Identified by Topographic Single Cell Sequencing. Cell\| PubMed ID: 29307488	2018
Genomic analysis defines clonal relationships of ductal carcinoma in situ and recurrent invasive breast cancer. Nature genetics\| PubMed ID: 35681052	2022
PCA-Plus: Enhanced principal component analysis with illustrative applications to batch effects and their quantitation. bioRxiv : the preprint server for biology\| PubMed ID: 38260566	2024

Anna K. Casasent

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