Penn Medicine technology facilitates rare mutation detection

Penn’s Center for Personalized Diagnostics uses cutting-edge, genome-wide tests to see the rare mutations even high-power microscopes cannot detect.

The CPD— a joint venture between the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center —began testing for patients on Feb. 14. It integrates Molecular Genetics, Pathology Informatics and Genomic Pathology, and uses cutting-edge, genome-wide tests to see the rare mutations even high-power microscopes cannot detect.

“On a day to day basis, we receive tumor specimens that the pathologists have already reviewed and … we extract the DNA from the samples we receive,” Robert Daber, the Technical Director of Clinical Genomics at the Center for Personalized Diagnostics said.

“We then sequence a large number of genes from the genome and look for mutations that are present in the tumor specimens that then help the clinicians understand how to treat their patients better.”

David Roth, chair of the department of Pathology and Laboratory Medicine, joined Penn almost two years ago and created CPD in close collaboration with Chi Dang of the Abramson Cancer Center.

“This technology, called massively parallel sequencing, or ‘next generation sequencing,’ allows us, for the first time, to determine the nucleotide sequences of many genes simultaneously,” he said in an email. “In our first few weeks of applying these tests, called cancer gene panels, we have already found mutations in samples from several patients that are very rare in those particular cancers, and would not have been looked for using single gene tests.”

Since CPD began operating two months ago, tests in 80 percent of patients revealed genetic mutations — findings that allow for more efficient treatment options.

The center currently focuses on four disease areas — acute myeloid leukemia, brain tumors, lung tumors and melanoma — but plans to expand tests to other diseases in the near future.

Director of the Leukemia Program at the Abramson Cancer Center Selina Luger explained that most patients with AML receive a standard treatment of induction chemotherapy to treat the disease. Once patients are in remission, they are given more chemotherapy to prevent the disease from returning.

Cytogenetics — which looks at the DNA of chromosomes — was discovered at Penn more than 50 years ago. However, this analysis does not detect abnormalities in the majority of patients.

“So the question is: is there a way to identify abnormalities in those patients with normal chromosomes? And that’s what the Center for Personalized Diagnostics is doing for us,” Luger said. “So far we’ve looked at about 30 patients with acute leukemia and 95 percent of them have had genetic abnormalities identified that were not done by traditional tests.”

She explained that the goal is to develop novel therapies that are less toxic and allow for treatment without the side effects that result from chemotherapy.

In addition to this goal, CPD is currently working on gene panel based tests that will hopefully be able to detect a variety of cancers via a simple blood test, according to Roth.

“It is thrilling for us to be able to offer new hope to patients. Our entire team is very gratified by our early experience. This is working out even better than we had hoped,” he said.

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