New findings from researchers at the Sloan Catering Memorial Cancer Center (MSK) published today in the journal The nature of communication report the results of using an integrated sequencing approach to 114 pediatric, adolescent, and young adult patients with solid tumors. The researchers found that their approach identified at least one additional oncogenic variant associated with cancer in 54% of patients (62 of 114) compared to the current standard genetic sequencing test MSK-IMPACT. Of these, 33 patients had one or more findings that had direct clinical or potentially applicable value.

DNA sequencing tests that detect mutations in cancer-related genes have become the standard of care in leading centers, including the MSK. MSK test, called MSK-Sigh, can detect mutations in more than 500 genes associated with cancer. Based on this information, physicians can determine whether an available drug can benefit a particular patient based on the genetic profile of the tumor.

This approach to the cancer gene panel works very well for adults with common types of cancers such as breast cancer, rectal cancer, lung cancer and prostate cancer. But for rare cancers in children and young adults, these panel tests were not as useful for selecting patients for appropriate therapy. This is because, as researchers come to understand, the types of mutations that cause tumors in young patients are usually different from mutations in young patients. adult patients.

“Cancer in adults is usually caused by a lifelong accumulation of mutations from exposure to things like sunlight, cigarette smokeand carcinogens in the diet, explains Andrew Kung, a scientist who chairs the MSK Department of Pediatrics and who studies the molecular causes of cancer in children. point mutations“Where one letter of DNA changes in a gene.”

«З pediatric cancer“,” He continues, “driving mutations are usually structural changes that affect entire sections of chromosomes. They are often outside of known cancer genes, where they go unnoticed by existing tests. ”

To better visualize these structural options, researchers need a way to read not only changes in the spelling of certain “words” or cancer genes, but also the organization of those words in the context of paragraphs and sections. This is what a technique called DNA and RNA sequencing of the entire genome provides, and Dr. Kung and his colleagues believe it could play an important role in caring for children with cancer.

“Everyone agrees sequencing of the entire genome will eventually become the primary diagnostic test for tumor profiling, “says MSK computing oncologist Eli Papaemmanuel.” But there were a few obstacles in the way. “

The biggest of them, she said, is the ability to make sense of the vast amount of data coming from a sequence of billions of letters of DNA that make up the whole genome-accurate definition and, accordingly, the transfer of the clinical condition relevant information to physicians in terms that can assist in making care decisions. In a published study, researchers refined the analysis of such data, which should be performed in a few days, compared to standard approaches that require weeks or months.

Not yet a replacement for another test

The researchers emphasize that the new platform is not currently a replacement for panel tests such as MSK-IMPACT, which work well to capture relevant mutations in adult patients with common tumors – and affect their results.

“What we are trying to do is bring a more comprehensive approach pediatric patients and others with rare cancers, a minority of whom use panel testing, “says Dr. Kung.” We want to make precision medicine more inclusive and accessible to every cancer patient. “

The study’s authors say the benefits for pediatric patients are so compelling that this type of testing is now available to every pediatric patient at MSK through charitable funding.