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

• Published in: Gynecologic oncology reports Vol. 24; pp. 94 - 98
• Main Authors: Martin, Madhuri, Sabari, Joshua K., Turashvili, Gulisa, Halpenny, Darragh F., Rizvi, Hira, Shapnik, Natalie, Makker, Vicky
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2018; Elsevier
• Subjects: Case Report; Immunotherapy; Multiple primary tumors; Next-generation sequencing; Tumor mutational burden; Tumor mutational burden; Next-generation sequencing; Immunotherapy; Multiple primary tumors
• ISSN: 2352-5789; 2352-5789
• DOI: 10.1016/j.gore.2018.04.004

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. 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. 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. •Multiple primaries are defined as more than one synchronous or metachronous cancers.•Next-generation sequencing can define the genetic landscape of multiple primaries.•Tumor mutational burden is a potential predictor of response to immunotherapy.•Management of multiple primaries is complex and requires multispecialty team care.