Clinical Sequencing Contributes to a BRCA-Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course

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  • a From the Departments of Obstetrics, Gynecology, and Reproductive Sciences, Medicine, Bioengineering and Therapeutic Sciences, Radiology and Biomedical Imaging, Pathology, Laboratory Medicine, and Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California; and (Present address) Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.
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Cancer is currently classified and treated using an approach based on tissue of origin. Ambiguous or incorrect diagnoses, however, are common and often go unnoticed. Clinical cancer sequencing can provide diagnostic precision, therapeutic direction, and hereditary cancer risk assessment. This report presents a patient with an initial diagnosis of metastatic pancreatic adenocarcinoma (PDA), a disease with a dismal prognosis. Tumor sequencing revealed genomic abnormalities inconsistent with PDA, instead suggesting serous ovarian cancer. This molecular rediagnosis was further refined by the identification of a BRCA2 truncating mutation in the tumor, subsequently confirmed to be a germline event. These findings prompted the initiation of platinum-based chemotherapy, which produced a life-altering response, and referral to genetic counseling for her offspring. These results suggest that clinical tumor sequencing can simultaneously clarify diagnoses, guide therapy, and inform familial risk, even in patients with end-stage metastatic disease, making the case for the development of specific strategies to deploy sequencing coupled with big data in oncology to improve clinical cancer management.

Correspondence: Eric A. Collisson, MD, Department of Medicine, Division of Hematology and Oncology, Helen Diller Family Comprehensive Cancer Center, 1450 3rd Street, San Francisco, CA 94158. E-mail:; Barry S. Taylor, PhD, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY 10065. E-mail:

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