On the trail of invasive cells in breast cancer

By Douglas S. Micalizzi & Shyamala Maheswaran

In the early-stage breast cancer called ductal carcinoma in situ (DCIS), a cluster of cancer cells arises in the milk duct and remains confined there. The recorded incidence of DCIS has risen since the late 1980s, probably due to an increase in its detection through more widespread breast-cancer screening1. Up to 40% of cases of DCIS progress to invasive ductal carcinoma (IDC), in which tumour cells invade other regions of the breast24. IDC requires clinical treatment. Moreover, because it is not possible to predict which people with DCIS are at risk of progressing to IDC, the standard treatment for patients who have DCIS is surgery, often followed by radiotherapy5. Therefore, understanding how DCIS progresses to IDC might enable the selective treatment of those at high risk of developing IDC. A paper in Cell by Casasent et al.6 reveals the origin of DCIS and its progression to IDC.

Casasent and colleagues obtained frozen samples of breast-cancer tissue gathered from patients. The authors used single-cell DNA sequencing of cells from DCIS and IDC regions in the same section of tissue to create molecular maps of patients’ breast cancers, in an approach they call topographic single-cell sequencing. They stained the samples to identify tumour cells and noted the location of each selected cell in the regions of DCIS and IDC. A technique called laser capture microdissection enabled the separation of a selected cell from its neighbours by tracing a laser beam around the cell. This was combined with an approach termed laser catapulting, in which energy from an ultraviolet laser propels a microdissected cell into a collection tube for subsequent DNA analysis. These laser-based techniques are used in other contexts, including forensic science and studies of plant physiology7.

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