Profile Tumor Cells from Small Samples

Photo: Cancer cells under the microscope

The genetic history of a tumor
cell is written in its DNA;
© NCI Visuals Online

The technique focuses on 'copy number variation' in cancer cells. These are changes to the number of copies of large sections of DNA. For example, genes that were thought always to occur in two copies per cell might sometimes be found in one, three or more copies.

Researcher James Hicks explained: "Most solid tumors exhibit varying degrees of chromosomal rearrangement. As cells progress from normal state where there are two copies of each chromosome, to become more cancer-like, they tend to accumulate more and more rearrangements that can be seen as copy number changes. The genetic history of a tumor cell is written in its DNA. Much of that information can be extracted from its copy-number profile."

Many rearrangements are characteristic of different cancer types or sub-types and are beginning to be used in diagnosis and prognosis. However, most tumor samples are mixtures of tumor cells of potentially different types mixed together with other tissue, making it difficult to understand what is going on in specific tumor cells.

The scientists recently published a method for enriching tumor cells from small parts of tumor specimens, separating them by virtue of their aberrant DNA content, and determining that the patterns were present in individual cells. Hicks reported that the researchers were able to use the technique to show the pathway of genetic changes that happened as two breast carcinomas developed.

"By profiling over 100 individual cells from a single tumor, we have obtained evidence that as cancer cells initiate their progression they undergo drastic changes, sometimes losing as much as 25 percent of their genomic DNA through deletions, yet are still able to establish clones of identical cells that occupy large portions of the tumor mass," Hicks explained.

"At least three major populations of cells, all genetically related, were found to occupy one particular tumor mass. We are now working to understand which of these cells can go on to form distant metastases."

Currently, these techniques are too expensive and time-consuming for routine use. "But we believe that the drastic increases in sequencing efficiency and sample multiplexing on the horizon will make this approach feasible in the near future," Hicks said.; Source: European Society for Medical Oncology