Cancer of unknown primary (CUP) is an enigmatic entity in which malignancy is histologically proven by a metastasis specimen, but the primary tumor remains elusive despite extensive clinical workup, including clinical examination; CT of the neck, chest, and abdomen; gastroscopy and colonoscopy; comprehensive laboratory analyses; and further tests dictated by the clinical picture of metastasis.1 Recently, clinical studies have used molecular panel sequencing with the hope that a better understanding of the molecular signatures might facilitate the allocation of the respective tumors to the most likely primary.2–5 Molecular profiling also offers the prospect and holds the promise of identifying mutations targetable by molecular therapies critically needed in this entity, due to its generally disappointing response to standard chemotherapy and overall dismal prognosis. Our center has implemented a strategy of performing routine molecular panel sequencing for patients with CUP. In patients with an antecedent or concurrent malignancy in which clonal relation to the CUP tumor is questionable, we have adopted a strategy for panel sequencing of both tumor specimens for comparison to address their clonal relationship.
The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
This work was supported by the Volkswagenstiftung (Lichtenberg program to M.R.S.) and by the German Cancer Consortium (DKTK; to P.S. and A.S.).
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