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Most Commonly Used Ovarian Cancer Cell Lines Do Not Resemble Ovarian Cancer

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Key Points

  • Using datasets from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia, researchers analyzed and ranked several cell lines by their genomic similarities to tissue samples and uncovered multiple discrepancies between the cell lines and actual human tumors.
  • The two most utilized cell lines for high-grade serous ovarian cancer, SK-OV-3 and A2780, were found to lack the TP53 mutations and substantial copy-number changes characteristic of this subtype.

Researchers from Memorial Sloan-Kettering Cancer Center recently discovered that the most frequently used cancer cell lines in ovarian cancer research are not suitable models of ovarian cancer. Their findings are the result of a detailed review of genomic data that recently became publicly available. Their methods, published in this week’s Nature Communications, could provide a usable framework for other researchers to better assess cell lines’ validity for future use in this and in other types of cancer research.

Study Details

Computational biologists Nikolaus Schultz, PhD, and Rileen Sinha, PhD, and biochemist Silvia Domcke, focused their review on high-grade serous ovarian cancer, the most commonly diagnosed and frequently studied subtype of ovarian cancer. Using datasets from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia, which detail and define the genomic features of numerous clinical samples and cell lines, the team analyzed and then ranked several cell lines by their genomic similarities to tissue samples and, in doing so, uncovered multiple discrepancies between the cell lines and actual human tumors.

“Our review showed that the two most utilized cell lines, accounting for almost 60% of all published research studies, do not resemble high-grade serous ovarian cancer well at all,” explained Dr. Schultz, the paper’s lead author. Key characteristics of high-grade serous ovarian cancer are TP53 mutations and substantial copy-number changes, but SK-OV-3 and A2780 both have a very flat copy-number profile and no TP53 mutations, instead having mutations frequently found in other histologic subtypes. “The problem with this is, investigators assumed they were studying high-grade serous ovarian cancer, when in reality they were looking at something else. So conclusions drawn from this work might be misleading,” Dr. Schultz said.

Implications

For the past several decades, in vitro tumor models have been the most popular model for the study of cancer because they are inexpensive and easy to replicate. However, the origin of some cell lines is not well established, and through years in culture, they can acquire additional changes, making them less desirable. Because of the lack of large-scale genomic data, identifying cell lines that most closely resemble the genomic alterations of a given tumor subtype has been difficult.

“With the explosion of genomic data now at our fingertips and the potential for more to become available, it’s our hope that this approach can be used by our colleagues to choose optimal cell lines, as we do expect similar discrepancies in other tumor types,” said Dr. Schultz. “Overall, we believe these findings should greatly benefit the study of cancer.”

The work was supported in part by a grant from the National Cancer Institute (NCI-U24CA143840).

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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