New cancer model shows genomic link between early-stage and invasive breast cancer types

January 04, 2018

HOUSTON -- new genetic-based model may explain how a common form of early-stage breast cancer known as ductal carcinoma in situ (DCIS) progresses to a more invasive form of cancer say researchers at The University of Texas MD Anderson Cancer Center.

The study provides new insight into how DCIS leads to invasive ductal carcinoma (IDC), and provides a clearer understanding of why some of these cancers go undetected. Findings were published in the Jan. 4 on-line issue of Cell. The discovery was made possible by the researchers' development of a new analytical tool called topographic single cell sequencing (TSCS).

"While DCIS is the most common form of early-stage breast cancer and is often detected during mammography, 10 to 30 percent of this type of cancer progresses to IDC," said Nicholas Navin, Ph.D., associate professor of Genetics. "Exactly how DCIS invasion occurs genomically remains poorly understood due to several technical challenges in tissue analysis."

The problem lies within the tumor itself, with cells that often have individual genetic characteristics, known as intratumor heterogeneity. Their unique cellular makeup makes treatment more difficult, while a low number of tumor cells in the breast milk ducts make the cells harder to spot due to their scarcity.

Navin's team found that genome evolution occurs in the ducts before cancer clones can be disseminated by "breaking through" the thin layer of tissue known as the basement membrane. They found that multiple cancer cell clones co-migrate from the ducts into adjacent regions to form invasive tumors.

Previous single cell DNA sequencing methods have emerged as powerful tools for understanding intratumor heterogeneity, but they delete information about individual tumor cells' precise location within the tissue. Cellular spatial data is critical for knowing whether tumor cells are DCIS or IDC. TSCS more accurately measures and describes specific characteristics of single tumor cells.

"Because TSCS provides spatial information on cell location, it represents a milestone over previous methods that can only use suspension of cells, therefore losing all spatial information," said Navin. "We hypothesized that invasive cells share a direct genomic lineage with one or more single cells in the ducts," he said. "Our data revealed a direct genomic lineage between both DCIS and IDC, and further showed that most mutations and DNA copy number aberrations evolved within the ducts, prior to invasion."

To arrive at these findings, Navin's team used exome sequencing and applied TSCS to 1,293 single cells from 10 patients with both DCIS and IDC.

"TSCS and other similar single cell sequencing methods hold great potential for opening new avenues of investigation in early stage cancers," said Navin. "It is our hope that this type of study will shed light on the enigmatic question of why some pre-malignant cancers do not progress while others become invasive."
-end-
Study team participants included Anna Casasent, Aislyn Schalck, Ruli Gao, Ph.D., Emi Sei, Ph.D., Annalyssa Long and William Pangburn, all of the Department of Genetics; Tod Casasent, Department of Bioinformatics & Computational Biology; Funda Meric-Bernstam, M.D., Department of Surgical Oncology; and Mary Edgerton, M.D., Ph.D., Department of Pathology.

The study was funded by the Lefkofsky Family Foundation, the National Cancer Institute (1R01CA169244-01 and CA016672); the American Cancer Society (129098-RSG-16-092-01-TBG); and the Chan-Zuckerberg Initiative (HCA-A-1704-01668).

University of Texas M. D. Anderson Cancer Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.