Genomic Evolution of Ductal Carcinoma In Situ: Clonal Models of Invasion
Understanding which ductal carcinoma in situ (DCIS) lesions will progress to invasive breast cancer remains a major clinical challenge. This review examines intratumour heterogeneity through three evolutionary models: independent lineages, evolutionary bottlenecks, and multiclonal invasion. The authors evaluate evidence from genomic profiling and discuss how emerging single-cell sequencing, STAR-FISH, and imaging mass spectrometry technologies could resolve the clonal architecture of DCIS progression and improve patient stratification.
The original study
Genome evolution in ductal carcinoma in situ: invasion of the clones.
- Authors
- Casasent AK, Edgerton M, Navin NE
- Journal
- The Journal of pathology
- Type
- Journal Article, Review
- PMID
- 27861897
Original abstract
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.