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Somatic Substitution Signature as an Innovative Tool in Lung Cancer Diagnosis
33 Pages Posted: 3 May 2019
More...Abstract
Diagnosis of lung cancer can sometimes be challenging and is of major interest since effective molecular-guided therapies are available. Compounds of tobacco smoke may generate a specific substitutional signature in lung, which is the most exposed organ. To predict whether a tumor is of lung origin or not, we developed and validated the EASILUNG (Exome And SIgnature LUNG) test based on the relative frequencies of somatic substitutions on coding non-transcribed DNA strands from whole-exome sequenced tumors. Data from 7,796 frozen tumor samples (prior to any treatment) from 32 TCGA solid cancer groups were used for its development. External validation was carried out on a local dataset of 196 consecutive routine exome results. The EASILUNG test demonstrated good calibration and good discriminative power with a sensitivity of 80% and a specificity of 94.3%. Similar results were obtained from external validation. This innovative test may be helpful in medical decision-making in patients with unknown primary tumors potentially of lung origin and in the diagnosis of lung cancer in smokers.
Funding Statement: The authors state: "No funding."
Declaration of Interests: The authors declare no conflicts of interest.
Ethics Approval Statement: All patients gave their consent and the study was approved by the CGFL ethical board.
Keywords: Lung Cancer; Diagnosis; Somatic Substitution; Score; Signature
Suggested Citation: Suggested Citation