Article by Barbara Toman

Genetic testing is like security-camera video of a break-in, providing essential clues to identify a culprit. In certain cancers, the "culprit" might be a rearrangement in a person's DNA, which genomic testing can capture.

But sometimes, like too-fuzzy security footage, conventional genetic testing can't provide a positive identification. For people with cancer, the stakes are high because pinpointing the chromosomal problem can lead to more effective treatment.

Mayo Clinic has developed a novel group of clinical tests that zoom in on a person's genome to characterize chromosomal rearrangements. The testing, developed in conjunction with the Center for Individualized Medicine (CIM) and available through Mayo Medical Laboratories, relies on a technique known as "mate pair sequencing."

Nicole Hoppman, Ph.D.

"Our mate pair sequencing testing can characterize almost any chromosomal rearrangement. We can finally answer questions about suspicious rearrangements of important genes," says Nicole Hoppman, Ph.D., a medical geneticist who helped develop the tests.

Mate pair sequencing is performed after initial testing indicates a chromosomal abnormality. "The initial chromosome studies can tell us where a chromosomal rearrangement is located but not the specific gene content of the rearrangement," Dr. Hoppman says.

Another test, known as fluorescence in situ hybridization (FISH), can provide that gene-level information. "But FISH studies isn't a genome-wide test, and we often have questions about more than one region of a person's genome," Dr. Hoppman says.

Mate pair sequencing provides genome-wide, gene-level information. The entire genome of a patient is sequenced, but analysis is restricted to regions where an abnormality was found. "Mate pair sequencing can clarify in a single test the abnormalities seen by chromosome or FISH studies," Dr. Hoppman says.

Personalized cancer therapy

Mate pair sequencing can directly impact patient care. One example at Mayo Clinic is a pediatric patient who experienced a relapse of B-cell acute lymphoblastic leukemia.

FISH studies indicated a disruption of a gene known as ETV6, which is common in many types of cancer. Genetic disruptions typically involve pairs of genes, and the effects of the disruption depend on both of the specific genes involved. ETV6 has many possible partners in cancer, and in this case chromosome and FISH studies couldn't identify the partner.

But mate pair sequencing did just that. The identified partnership is rare yet can be treated with a certain class of cancer therapy. "The mate-pair result led to additional treatment options for the patient," Dr. Hoppman says.

Mayo Clinic's mate pair sequencing tests are designed to detect chromosomal rearrangements not only in leukemia but also in various types of lymphoma, certain solid-tumor cancers and inherited abnormalities. This testing is more efficient than other genomic sequencing strategies because it uses larger pieces of DNA as input material. Analyzing this type of data requires a sophisticated algorithm, which CIM researchers spent years developing.

As a whole-genome test, mate pair sequencing can keep pace with ongoing advances in individualized medicine. "If researchers make a new discovery that a gene is important, and a person has already had mate pair sequencing, we have all the data we need," Dr. Hoppman says. "We can go back and analyze another region in the person's genome.

"Mate pair sequencing is nimble," she adds. "It allows us to add targets and answer patients' questions faster when there's a new discovery. Better answers can lead to better treatment."

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Tags: #genomic testing, Cancer, cancer genomics, Chromosomal rearrangement, Mayo Clinic Center for Individualized Medicine, mayo medical laboratories, Nicole Hoppman, Ph.D., Precision Medicine, Rare diseases