Carcinoma of unknown origin: Deep genomic profile helps to achieve an accurate diagnosis

      Background: Diagnosis and treatment of Cancer of Unknown Origin (CUP) continues to be a challenge. In the era of personalized medicine, genomic profile by Next-Generation-Sequencing (NGS) in addition to immunohistochemistry (IHC) tests may complement clinical features improving diagnosis and detecting targetable mutations. In the present study we have analysed the clinical utility of theOncoDEEP® CUP platformfor tissue of origin assessment and genotyping in a cohort of CUP patients.
      Methods: We conducted this multicentric prospective exploratory study across 22 institutions (September 2017- March 2018). The cohort included 60 patients with histologically diagnosed metastatic CUP and available FFPE tumor samples. The molecular analysis was performed using the OncoDEEP® CUP platform, which includes a deep genomic tumor characterization as well as a panel of IHC tests.
      Results: Patient’s median age was 60 years [24-80], 61.7% were females. At time of diagnosis,48% presented a single metastatic site whereas 52% has multimetastaticlocations. Predominant histology was adenocarcinoma (36.7%) followed by carcinoma NOS (25%), squamous cell carcinoma (13.3%) and others (25%). In 10% of the cases, the analysis could not be completed due to insufficient tumor samples. In the remaining 54 samples, a probable primary origin was assessed in 43 patients (80%). Potentially actionable mutations were found in 36 cases (61%). As expected, the most frequently mutated gene was TP53 (12/36), followed by KRAS, TPMT, ARID1A,BRAF, CDKN2A, PI3KCA, PTEN and STK11. During follow up 11 deaths have been recorded, whereas the rest of the patients remain in the study.
      Conclusions: OncoDEEP® CUP may provide an opportunity for CUP patients to benefit from site-specific treatments and personalized therapies if druggable mutations are identified. Acknowledgments to the rest collaborating centers: H. U. de Ceuta, H. U. Virgen Macarena, H. Ramón y Cajal, H. U. Santa Lucía, HC Marbella International Hospital, H. Parc Taulí, H. U. La Ribera, H. Marina Baixa, H. Morales Meseger, H. U. Lucus Augusti and Instituto Valenciano de Oncología (IVO).
      Legal entity responsible for the study: Hospital General Universitario de Valencia, Valencia, Spain, Valencia.
      Funding: The Spanish Institute for Foreign Trade (ICEX).
      Disclosure: A. Terradez, A. Rodrigo, L. Alvarez, G. Beniuga: Employee: OncoDNA. All other authors have declared no conflicts of interest.