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


Authors: Martin, M.; Sabari, J. K.; Turashvili, G.; Halpenny, D. F.; Rizvi, H.; Shapnik, N.; Makker, V.
Article Title: Next-generation sequencing based detection of germline and somatic alterations in a patient with four metachronous primary tumors
Abstract: 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. © 2018 The Authors
Keywords: cancer survival; clinical article; human tissue; primary tumor; overall survival; somatic mutation; case report; cancer staging; sentinel lymph node biopsy; cancer susceptibility; ipilimumab; melanoma; computer assisted tomography; mutational analysis; genome analysis; immunotherapy; mismatch repair; microsatellite instability; brain metastasis; carcinomatous peritonitis; anastrozole; genetic predisposition; nuclear magnetic resonance; clinical observation; lumpectomy; bronchus carcinoid; lung nodule; metastatic melanoma; wide excision; germline mutation; multiple primary tumors; next generation sequencing; cancer prognosis; estrogen receptor positive breast cancer; next-generation sequencing; nivolumab; human; female; priority journal; article; pembrolizumab; positron emission tomography-computed tomography; progesterone receptor positive breast cancer; gallium dotatate ga 68; tumor mutational burden; metachronous primary tumor
Journal Title: Gynecologic Oncology Reports
Volume: 24
ISSN: 2352-5789
Publisher: Elsevier B.V.  
Date Published: 2018-05-01
Start Page: 94
End Page: 98
Language: English
DOI: 10.1016/j.gore.2018.04.004
PROVIDER: scopus
PMCID: PMC6003430
PUBMED: 29915805
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Vicky Makker
    76 Makker
  2. Joshua K Sabari
    21 Sabari
  3. Hira Abbas Rizvi
    20 Rizvi
  4. Madhuri Martin
    3 Martin