Targeted sequencing identifies the mutational signature of double primary and metastatic malignancies: a case report

Chuangzhou Rao,Analyn Lizaso,Xiaobo Miao,Guofang Zhao,Liangqin Nie

doi:10.1186/s13000-019-0874-5

Chuangzhou Rao, Analyn Lizaso + Show 3 more

Open Access

https://doi.org/10.1186/s13000-019-0874-5

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Abstract

BackgroundThe accurate identification of the tissue of origin is critical for optimal management of cancer patients particularly those who develop multiple malignancies; however, conventional diagnostic methods at times may fail to provide conclusive diagnosis of the origin of the malignancy. Herein, we describe the use of targeted sequencing in distinguishing the primary and metastatic tumors in a patient with metachronous malignancies in the lung, colon and kidney.Case presentationIn December 2016, a 55-year-old Chinese male was diagnosed with stage IB lung adenosquamous carcinoma and treated with left lower lobectomy and 4 cycles of platinum-based chemotherapy. After being disease-free for 3.5 months, three colonic polyps were discovered and were diagnosed as invasive adenocarcinoma after polypectomy. Within 5.4 months from the polypectomy, squamous cell renal carcinoma was identified and was managed by radical nephrectomy. Immunohistochemistry results were inconclusive on the origin of the kidney tumor. Hence, the three archived surgical tissue samples were sequenced using a targeted panel with 520 cancer-related genes. Analysis revealed similar mutational signature between the lung and kidney tumors and a distinct mutational profile for the colon tumor, suggesting that the lung and colon malignancies were primary tumors, while the kidney tumor originated from the lung, revealing a diagnosis of metastatic double primary cancer – lung carcinoma with renal cell metastasis and second primary colon carcinoma.ConclusionMutational profiling using targeted sequencing is valuable not only for the detection of actionable mutations, but also in the identification of the origin of tumors. This diagnostic approach should be considered in similar scenarios.

Highlights

The accurate identification of the tissue of origin is critical for optimal management of cancer patients those who develop multiple malignancies; conventional diagnostic methods at times may fail to provide conclusive diagnosis of the origin of the malignancy
Mutational profiling using targeted sequencing is valuable for the detection of actionable mutations, and in the identification of the origin of tumors. This diagnostic approach should be considered in similar scenarios
The patient we described in this report was fortunate with the repeated incidental discovery of his lung and colon tumors at their early stage, he only survived less than 2 years from the time of the diagnosis of the first cancer

Summary

Background

The accurate diagnosis of the tissue of origin and cancer type is critical in guiding the optimal management and improving the treatment outcome of cancer patients with multiple malignancies. We describe the application of capture-based targeted sequencing in distinguishing the origin of the metachronous malignancies in the lung, colon and kidney of our patient. On August 2017, chest CT revealed no disease recurrence in the lungs (Fig. 1a); colonic polyps were discovered during his physical examination. A total of 16, 15 and 7 mutations were detected in the lung, kidney and colon tumor samples, respectively (Table 2). Except for the FANCC W113X and KMT2C S321 N common to the three tumor samples, no other mutations were shared between the colon and either the lung or the kidney tumor samples (Fig. 2a). The patient passed away on August 2018 due to severe infection, with an overall survival of 20.4 months

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Conclusion