Next-generation sequencing based detection of germline and somatic alterations in a patient with four metachronous primary tumors

• Main Authors: Madhuri Martin, Joshua K. Sabari, Gulisa Turashvili, Darragh F. Halpenny, Hira Rizvi, Natalie Shapnik, Vicky Makker
• Format: Article
• Language: English
• Published: Elsevier 2018-05-01
• Series: Gynecologic Oncology Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2352578918300286

Introduction: Multiple primary tumors (MPTs) are defined as two or more separate synchronous or metachronous neoplasms occurring in different sites in the same individual. These tumors differ in histology, as well as primary sites from which they arise. Risk factors associated with the occurrence of MPTs include germline alterations, exposure to prior cancer therapies, occupational hazards, and lifestyle and behavioral influences. Case report: We present a case of a patient who was diagnosed with four metachronous primary tumors. In 2013, she was diagnosed with serous proliferations associated with psammomatous bodies of primary peritoneal origin (pT3NxM0). This was followed by invasive ductal carcinoma of the breast (stage pT2N0Mx, histological grade III/III) in 2014, melanoma (stage pT2bNxMx) in 2016 that further advanced to the lung and brain in 2017, and a low-grade lung carcinoid in 2017. To better understand the biology of this patient's MPTs, we performed next-generation sequencing (NGS) to assess for both somatic and germline alterations. The treatment course for this patient aims to target the tumor with the strongest prognostic value, namely her malignant melanoma, and has contributed favorably to the overall survival of this patient. Conclusion: We report the clinical and genomic landscape of a patient with MPTs who had no identifiable unique somatic or germline mutations to explain her predilection to cancer. The treatment course and overall prognosis for this patient is important for understanding future cases with unrelated, metachronous MPTs, the occurrence of which cannot always be explained by underlying genetic mechanisms. Keywords: Multiple primary tumors, Next-generation sequencing, Tumor mutational burden, Immunotherapy