Molecular medicine tumor board: whole-genome sequencing to inform on personalized medicine for a man with advanced prostate cancer.

Armstrong, Andrew J; Li, Xiaotong; Tucker, Matthew; Li, Shantao; Mu, Xinmeng Jasmine; Eng, Kenneth Wha; Sboner, Andrea; Rubin, Mark; Gerstein, Mark (2021). Molecular medicine tumor board: whole-genome sequencing to inform on personalized medicine for a man with advanced prostate cancer. Prostate cancer and prostatic diseases, 24(3), pp. 786-793. Springer Nature 10.1038/s41391-021-00324-5

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PURPOSE

Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain.

PATIENT AND METHODS

We present a case of whole-genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available.

RESULTS

We describe an 84-year-old Caucasian male with a Gleason 10 oligometastastic hormone-sensitive prostate cancer. Whole-genome sequencing provided insights into his tumor's underlying mutational processes and the development of an SPOP mutation. It also revealed an androgen-receptor dependency of his cancer which was reflected in his durable response to radiation and hormonal therapy. Potentially actionable genomic lesions in the tumor were identified through a personalized medicine approach for potential future therapy, but at the moment, he remains in remission, illustrating the hormonal sensitivity of his SPOP-driven prostate cancer. We also placed this patient in the context of a large prostate-cancer cohort from the PCAWG (Pan-cancer Analysis of Whole Genomes) group. In this comparison, the patient's cancer appears typical in terms of the number and type of somatic mutations, but it has a somewhat larger contribution from the mutational process associated with aging.

CONCLUSION

We combined the expertise of medical oncology and genomics approaches to develop a molecular tumor board to integrate the care and study of this patient, who continues to have an outstanding response to his combined modality treatment. This identifiable case potentially helps overcome barriers to clinical and genomic data sharing.

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