New Analytical Tool May Determine How DCIS Invasion Occurs

January 16, 2018
John Schieszer

A new analytical tool called topographic single-cell sequencing can reveal a direct genomic lineage between in situ and invasive tumor subpopulations, which may help decipher how and why some DCIS become invasive.

Oncologists soon may have a new tool for improving outcomes in women with ductal carcinoma in situ (DCIS). In a study published online January 4, 2018 in the journal Cell, researchers at University of Texas M. D. Anderson Cancer Center (MDACC) report they have developed a new analytical tool called topographic single-cell sequencing (TSCS), which can reveal a direct genomic lineage between in situ and invasive tumor subpopulations. The study also demonstrated that most mutations and copy number aberrations evolved within the ducts prior to invasion.

Researcher Nicholas Navin, PhD, who is an associate professor of genetics at MDACC, said DCIS is the most common form of early-stage breast cancer and is often detected during mammography. However, 10% to 30% of DCIS cases progress to invasive ductal carcinoma (IDC). Until now, he said exactly how DCIS invasion occurs genomically was poorly understood due to a host of technical challenges in tissue analysis.

TSCS can measure genomic copy number profiles of single tumor cells and preserve their spatial context in tissue sections. This analytical tool combines laser-capture-microdissection, laser-catapulting, whole-genome-amplification (WGA), and single-cell DNA sequencing. Laser-catapulting is a touchless approach that transfers cells using ultraviolet energy, eliminating potential bacterial contamination and adjacent cell contamination compared with standard systems, which require physical contact with the tissues.                                                                                                                                                                                                                                                                                                                                Navin and his colleagues applied TSCS to 1,293 single cells from 10 synchronous patients with both DCIS and IDC regions and combined this with exome sequencing. They found there was a multiclonal invasion where one or more clones escaped the ducts and migrated into the adjacent tissues to establish invasive carcinomas.

Naoto Tada Ueno, MD, PhD, who is section chief of translational breast cancer research in the Department of Breast Medical Oncology at MDACC, said these findings are a crucial first step. “Understanding this progression pattern is important. This could help decipher the mechanism and give us ideas on how to prevent it,” Dr. Ueno told Cancer Network. “This is an area that we really need to understand.”

Navin’s team found that genome evolution occurs in the ducts before cancer clones can be disseminated. He said previous single-cell DNA sequencing methods did not have information about the precise location of an individual tumor cell within the tissue. However, TSCS overcomes this obstacle. Navin said because TSCS provides spatial information on cell location, it represents a significant advance over previous methods.

TSCS may also be useful when looking at other tumor types. Navin said TSCS and other similar single-cell sequencing methods hold great potential for opening new avenues of investigation in many early-stage cancers. In addition, it is hoped that this new analytical tool may be able to explain why some premalignant cancers do not progress while others become invasive. “There is some kind of genetic convergence that is happening and we need to know how it is happening. We may be able to intervene and stop the process,” said Dr. Ueno.