ASCO 2015: Tumor Sequencing Study Highlights Benefits of Profiling Healthy Tissue
As the practice of genetically profiling patient tumors for clinical treatment decision-making becomes more commonplace, a recent study from The University of Texas MD Anderson Cancer Center suggests that profiling normal DNA also provides an important opportunity to identify inherited mutations that could be critical for patients and their families.
Preliminary findings from this ongoing study were presented by Funda Meric-Bernstam, MD, Professor and Chair of MD Anderson’s Department of Investigational Cancer Therapeutics, on June 1 at the 2015 ASCO Annual Meeting (Abstract 1510).
Benefits of Sequencing Nontumor DNA
The MD Anderson research team sequenced tumor and normal DNA from patients with advanced cancer, with the goal of sharing results with patients to better educate them going forward. Sequencing normal tissue is not routinely done in the research environment, but comparing tumor vs normal DNA can distinguish between germline mutations and those found only in the tumor.
“This is an opportunity to identify germline mutations that could have contributed to a patient’s cancer development and may be a heritable cancer syndrome that would put the patient’s family members at risk,” said Dr. Meric-Bernstam, who is also Medical Director of the Khalifa Institute for Personalized Cancer Therapy. “Therefore, it would be important to inform the patients and their family members so they can get further testing, genetic counseling, and begin risk-reducing efforts as needed.”
Study Details
In this study, researchers performed targeted sequencing of 202 genes, including a panel of 19 genes for which mutations are implicated as a significant cancer risk. The American College of Medical Genetics and Genomics recommends that harmful mutations in these genes, including TP53, BRCA1, BRCA2, PTEN, and RB1, be shared with patients because of that risk. Of the 1,000 patients analyzed, 99.9% had at least 1 germline variant in 1 of these 19 genes.
Further analysis revealed 43 of these patients had mutations considered likely to be pathogenic. Importantly, more than half (23) of these patients were previously not known to have mutations, highlighting the utility of this approach. All mutations were confirmed in a clinical laboratory, with 100% agreement.
Although the data are valuable to the care of patients, not all research protocols take into account how best to share this information, explained Dr. Meric-Bernstam. In this study, 99% of patients said they would like to be informed of harmful mutations. Those with pathogenic germline mutations are now being brought back for formal genetic counseling, a critical component of the study.
Benefit to Relatives
“Patients have been very interested and, overall, grateful to be part of this protocol, recognizing the importance of this finding, especially for their families,” said Dr. Meric-Bernstam.
Once family members are made aware of the possibility of harmful inherited mutations, they can get tested for specific mutations in the gene(s) in question. Depending on those results, they can enroll in high-risk screening programs that may detect the disease early and may offer risk-reduction measures.
Dr. Meric-Bernstam does not suggest all cancer patients should have their tumors sequenced. But for those already having sequencing performed, she said, “It is important to consider analyzing the normal data as well in order to capitalize on the opportunity to inform the patients and their families of the findings.”
Going forward, the research team will complete analysis of additional patients included in the study to identify those with potentially harmful mutations and build upon their experience in reporting those results to clarify the best way to utilize data obtained from this approach.
This work was supported by the Khalifa Bin Zayed Al Nahyan Foundation, the National Center for Advancing Translational Sciences, the Bosarge Foundation, and the MD Anderson Cancer Center Support Grant. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
