Detecting tumour cells individually

May 16, 2012 By Peter Rüegg, ETH Zurich
Detecting tumour cells individually
A tumour consists of more different genetic variants of cancer cells (in the picture, a lung-cancer cell) than originally believed. Credit: Wellcome Images / Flickr

(Medical Xpress) -- Swiss researchers have devised a method to detect mutations in tumor cells that are only present in a proportion of the cancer’s cells. The analysis reveals that cells of individual tumours are more variable than first thought – and differ from patient to patient.

Sometimes, a tumor only develops very slowly. It begins with a few cells that mutate. Then these cells mutate. And mutate again. The mutants are more successful than their predecessors, outcompeting them as they multiply. Consequently, new variants of cells keep emerging, each fitter than their predecessors: the tumor goes through an evolution that gives rise to a genetically heterogeneous .

This makes it difficult to treat a tumour with medication as there might be cells that do not respond to the drug used. Researchers from ETH Zurich and the Swiss Institute of Bioinformatics thus teamed up with colleagues from the University of Zurich to develop a new method for determining the genetic variants of reliably. Using this method, the researchers are able to detect mutations that only appear in one in every 10,000 cells.

Test on renal cancer tissue successful

“This method will be important for use in clinics, for instance, when therapy-resistant cell types need to be detected to adapt the treatment accordingly,” says lead author Moritz Gerstung from ETH Zurich’s Department of Biosystems Science and Engineering. The study has just been published in Nature Communications.

The new approach also enables to measure the frequency of certain variants within the tumour-cell population, which sheds light on how tumours grow and how quickly they change genetically inside the patient.

In a comparison of two particular regions of two genes from healthy renal cells and cells, the researchers found twenty-four gene variants. Some variants were only present in two in every 10,000 cells examined; others, however, in over a third.

Statistics compensate for read errors

For their method, the researchers genetically analyzed countless tumor cells from renal cancer tissue using a modern sequencing technique called “deep sequencing”. As a result, millions of DNA fragments from single genes were sequenced simultaneously. These DNA fragments are isolated from the entire population of tumor cells and shed light on the genetic composition of the tumor. These genes were sequenced over 100,000 times, which corresponds to equally as many individually sequenced cells.

In reading the genetic code, however, errors can occur. So as not to mistake these errors for actual mutations, the researchers sequenced healthy tissue in parallel to be able to determine the error rate at any point on the DNA. In order to distinguish actual mutations from sequencing errors at a particular point, they developed a special statistical algorithm. “This was a critical step for us as even the tiniest of inaccuracies can cause a large number of errors because the algorithm analyses several million DNA fragments,” says Dr. Gerstung.

Personalized cancer medicine the aim

The researchers began by testing their new method on control samples with a known cell composition to make sure that it worked and did not display any false forecasts. Then they analysed four tumor samples and found numerous or subtypes . “Their existence supports the theory that tumours change constantly in accordance with a Darwinian evolutionary process,” says Dr. Gerstung.

The new method helps personalise cancer therapy further. In future, tumors may not be treated as a unit. If one knows which cell types a tumor contains, the therapy can be adapted individually to a specific combination of drugs. When and whether the method will be used routinely in clinics remains to be seen. Further research is required to determine how tumor cell populations respond to different treatments. “However, the method is already at a stage where it can be also used for other cancer types,” says the ETH-Zurich researcher.

Explore further: New analytical method enhances the possibility of selecting optimal cancer treatment

More information: Gerstung M, Beisel C, Rechsteiner M, Wild P, Schraml P, Moch H & Beerenwinkel N. Reliable detection of subclonal single-nucleotide variants in tumour cell populations. Nature Communications, published online on 2 May 2012. doi: 10.1038/ncomms1814

Related Stories

New analytical method enhances the possibility of selecting optimal cancer treatment

November 14, 2011
For a cancer treatment to be adapted to each individual patient, a large number of tumor samples need to be examined carefully. Collaboration between a company and Uppsala University has now led to a method that makes this ...

An ABSOLUTEly new view of the cancer genome

May 4, 2012
(Medical Xpress) -- Scientists hoping to unlock cancer’s secrets face a formidable challenge. Sophisticated research tools have allowed them to peer into the genomes of cancer cells and identify many DNA alterations ...

Sensitive detection method analyzes circulating tumor cells in patients with lung cancer

January 9, 2012
Researchers have developed a method to analyze circulating tumor cells in the blood of patients with non-small cell lung cancer. This method, which can analyze a sample size as small as three cells, may allow clinicians to ...

Scientists discover how cancers generate muscle-like contractions to spread around the body

August 16, 2011
Cancer Research UK-funded scientists have discovered that a protein called JAK triggers contractions in tumors which allows cancer cells to squeeze though tiny spaces and spread, in research published in Cancer Cell today.

DNA sequencing lays foundation for personalized cancer treatment

April 1, 2012
Scientists at Washington University School of Medicine in St. Louis are using powerful DNA sequencing technology not only to identify mutations at the root of a patient's tumor – considered key to personalizing cancer ...

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.