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UT Southwestern Genetics Program is Detecting “Mystery” Cancer Patients
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UT Southwestern Genetics Program is Detecting “Mystery” Cancer Patients

December 29th, 2014 Maureen Newman 0 comments

shutterstock_187967735At UT Southwestern‘s Cancer Genetics Clinic, researchers are looking to use whole-genome sequencing to predict and  prevent cancer. Approximately 5-10% of cancers are caused by inherited gene mutations, which can be detected by analyzing patients’ DNA.

“Whole-genome sequencing is a new genetic tool that can determine more of a person’s DNA sequence than ever before,” said Dr. Theodora Ross, Professor of Internal Medicine and Director of the Cancer Genetics Program, in a news release from the university.

Dr. Ross was the principal investigator of a new study published in EBioMedicine, “Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.” During this study, Dr. Ross’ team evaluated 258 cancer patients’ genomes for BRCA mutations, which have been implicated in breast cancer, and non-BRCA mutations, which include ATM, CDH1, CHEK2, PALB2, PTEN, and TP53 in the case of breast cancer.

“Our results show that nearly 90 percent of clinically identified mutations were confidently detected and additional cancer gene mutations were discovered, which together with the decreasing costs associated with whole-genome sequencing means that this method will improve patient care, as well as lead to discovery of new cancer genes,” said Dr. Ross. In a clinical setting, finding these mutations could allow a physician to counsel a patient on how to detect or prevent the cancer associated with the present mutations.

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Joining Dr. Ross were co-first authors Samantha Foley and Dr. Jonathan Rios. Together, they devised a new method to compare patients with BRCA1 or BRCA2 mutations to those without BRCA mutations. At least 88.6% of BRCA mutations were correctly identified in the whole-genome sequencing data, and some new cancer gene mutations were detected in the non-BRCA cohort.

These results would be especially useful for patients with non-BRCA mutations, or so-called “mystery patients,” according to Dr. Ross. “Mystery patients are those who have a strong family history for cancer but after standard genetic testing, no genetic diagnoses are made. In our study, sequencing allowed  us to discover novel candidate cancer gene mutations in mystery patients,” she said.

The study will add to the wealth of knowledge held at the Cancer Genetics Clinic, where patients are assessed for their risk for kidney, skin, lung, breast, ovarian, colon, endocrine, prostate, and many other cancers. By using whole-genome sequencing and methods to find mutations within the genome, Dr. Ross may enable better cancer detection and prevention in the future.

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Maureen Newman

Maureen Newman is a PhD student studying biomedical engineering at University of Rochester, working towards a career of research in biomaterials for drug delivery and regenerative medicine. She is an integral part of Dr. Danielle Benoit's laboratory, where she is investigating bone-homing therapeutics for osteoporosis treatment.

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