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Michigan's Oncology Sequencing Program, or MiOncoSeq, was the first of its kind in the nation to sequence patient tumors. Launched in 2010, the program analyzes DNA and RNA from normal tissue and tumors to identify alterations that could help guide treatment.

In a new study published in Cancer Discovery, U-M researchers have enhanced the process with long-read nanopore sequencing, which can detect alterations that might be missed by conventional sequencing.

Conventional short-read sequencing examines small pieces of DNA, typically a few hundred DNA letters long. Long-read sequencing can read thousands to tens of thousands of letters in a single stretch, allowing researchers to see complex changes and how they fit together.

"Having a list of mutations doesn't always explain a tumor," said Arul Chinnaiyan, M.D., Ph.D., S.P. Hicks Professor of Pathology and Urology, director of the Michigan Center for Translational Pathology and a Howard Hughes Medical Institute investigator. "We need to understand how these mutations are arranged, which conventional sequencing often cannot resolve."

Most genes come in two copies, one inherited from each parent. Nanopore sequencing can help clinicians understand whether one or both copies of a gene that protects against cancer are disabled. This can occur through complex DNA rearrangements and chemical modifications.

It can also show whether multiple mutations occur together on a single copy of a cancer-promoting gene, potentially increasing its activity or contributing to drug resistance.

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