Incidental germline findings offer 'remarkable advances,' raise ethical questions

CORONADO, Calif. — As genetic tumor testing becomes increasingly common, complex ethical questions are being raised when certain mutations, known as germline findings, are incidentally discovered, according to a plenary presenter here.

Mark E. Robson, MD, clinic director of Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center in New York, explained that germline findings can indicate conditions that can be passed onto later generations. This raises the complex ethical and medico-legal question as to whether or not to inform the patient, according to Robson.

Mark E. Robson

“There are many variables to consider, such as whether the [original] testing was for clinical or research purposes, the individual preference of the patient involved, whether anything can be done to control risk, and whether other people — such as close relatives — may be affected,” Robson said.

Robson explained that although the intent of tumor mutational profiling is to identify somatic variants, one complication of DNA sequencing of tumors is that the DNA in the tumor is the same as the DNA that was present when the individual was born.

“When you’re sequencing a tumor, you’re also sequencing the individual,” he said. “This can give you germline findings in two different ways: indirectly found mutations and simultaneously looking at the tumor. When you’re doing a germline sequence you’re directly evaluating constitutional DNA and you can much more directly identify variants.”

According to Robson, new studies, especially in oncology, are using DNA profiling to move beyond the traditional boundaries of histopathology and imaging and are incorporating a knowledge of the genetic mutations that are present in different cancers into treatment, as certain germline variants predict response to specific treatments.

“On the clinical side, what we want to do is identify somatic variants that are already known to be linked to a response to FDA-approved drugs,” Robson said. “By doing the profiling one would find, for instance, that a BRAF mutation would allow you to treat a melanoma patient with a BRAF inhibitor. … We hope this will allow us to improve treatment outcomes and, hopefully, reduce toxicity.”

Similarly, in the investigational setting, profiling is being performed to try to identify new clinical trials that would be appropriate for patients in both academic and non-academic settings. “Ultimately I think what the public hopes for and what we hope for is that we’ll be able to, by profiling, customize treatment for individuals,” Robson said. “We’ll be able to pull things off the shelf and mix and match to give the appropriate therapy for a specific person’s genetic mutational profile.” — by Amber Cox

For more information:

Robson ME. Clinical, ethical and legal implications of incidental germline findings discovered as part of sequencing studies. Presented at: American Thyroid Association Annual Meeting; Oct. 29-Nov. 2, 2014; Coronado, Calif.