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Food for Thought: Why tissue sample quality matters for personalized medicine

“We now have the technical ability to get the wrong answers with unprecedented speed.” Carolyn Compton, Director, Office of Biorepositories and Biospecimen Research

When the U.S. National Cancer Institute recently started its Cancer Genome Atlas initiative and asked biobanks all over the world for cancer biopsy samples, it was puzzled to find that the quality of the donated samples was so poor that the NCI was unable to meet the moderate target of collecting 1,500 biopsy samples per cancer. In a telling article in “Wired magazin”, Steve Silberman gives the example of a university biobank, which claimed to have more than 12,000 samples of glioblastoma in its collection. However, the initiative judged only 18 of those as good enough to use. After contacting biobanks on a global scale, the researchers did not even get to 500 glioblastoma samples of satisfactory quality and barely got to 500 in ovarian cancer, the 5th most common cancer in women. In lung cancer, the initiative was unable to start because it simply could not obtain the minimum number of biopsy samples of adequate quality. „However, all biobanks thought they were doing a superb job,“ resumed Carolyn Compton, director of NCI‘s Office of Biorepositories and Biospecimen Research OBBR and responsible for the biopsy sampling part.
The reason for the poor quality is simple: minutes after cutting tissue off from blood supply, cells start to react with massive changes in gene methylation patterns, gene expression and translation, proteome composition, enzymatic activities, surface protein patterns, etc. The changes affect hundreds of genes, and it is reality in many hospitals that the resected cancer tissue lies around for hours at room temperature in the operation theater before it is put in the freezer to get formalin-fixed a few days later.
Even more, the medication the patient has been given prior to or during operation (sedatives, anesthetics, etc.) has a profound impact on these parameters as well.
Therefore, very often it is impossible to judge whether the changes observed between individual patients is a result of their inherently different metabolisms/genetic makeup or a consequence of different sampling and handling of the biopsies and medications.
“We now have the technical ability to get the wrong answers with unprecedented speed,” Compton says. “If we put the wrong stuff into the front end of our analytical pipeline, we will not only lose the war on cancer, we’ll pollute the scientific literature with incorrect data that will take us a long time to sort out. This is a crisis that requires disruptive innovation.”
OBBR is now systematically looking into the problem and has chosen one company to perform the first systematic studies: Hamburg-based Indivumed GmbH. The company did pioneering research and devised standards for cancer biopsy samplings that are applied in a network of clinics Indivumed is collaborating with in the Hamburg and the Washington DC area. The company runs the only ISO-certified biobank in the world and is offering biospecimens, related patient data, and services including biomarker development for the purpose of developing personalized cancer therapies. By employing specially trained nurses, the company guarantees that each sample is frozen or fixed within 12 minutes, and each sample comes with a data package comprising several hundred data on the patient‘s medical history and life style. Further information about Indivumed, a client of akampion, can be found here.