title: Mutational Profile from Targeted NGS Predicts Survival in LDCT Screening-Detected Lung Cancers.
abstract: The issue of overdiagnosis in low-dose computed tomography (LDCT) screening trials could be addressed by the development of complementary biomarkers able to improve detection of aggressive disease. The mutation profile of LDCT screening-detected lung tumors is currently unknown.
  
  
  
  Targeted next-generation sequencing was performed on 94 LDCT screening-detected lung tumors. Associations with clinicopathologic features, survival, and the risk profile of a plasma microRNA signature classifier were analyzed.
  
  
  
  The mutational spectrum and frequency observed in screening series was similar to that reported in public data sets, although a larger number of tumors without mutations in driver genes was detected. The 5-year overall survival (OS) rates of patients with and without mutations in the tumors were 66% and 100%, respectively (p = 0.015). By combining the mutational status with the microRNA signature classifier risk profile, patients were stratified into three groups with 5-year OS rates ranging from 42% to 97% (p < 0.0001) and the prognostic value was significant after controlling for stage (p = 0.02).
  
  
  
  Tumor mutational status along with a microRNA-based liquid biopsy can provide additional information in planning clinical follow-up in lung cancer LDCT screening programs.
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Tumour Genomics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Verri
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Tumour Genomics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Borzi
authors.affiliation: Gensignia Life Sciences, Inc., San Diego, California.
authors.forename: Todd
authors.initials: T
authors.lastname: Holscher
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dugo
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Devecchi
authors.affiliation: Gensignia Life Sciences, Inc., San Diego, California.
authors.forename: Katherine
authors.initials: K
authors.lastname: Drake
authors.affiliation: Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sestini
authors.affiliation: Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Suatoni
authors.affiliation: Gensignia Life Sciences, Inc., San Diego, California.
authors.forename: Elisa
authors.initials: E
authors.lastname: Romeo
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Tumour Genomics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: gabriella.sozzi@istitutotumori.mi.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sozzi
authors.affiliation: Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pastorino
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Unit of Tumour Genomics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Boeri
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor
keywords: Low-dose computed tomography; Lung cancer; MicroRNA-based liquid biopsy; Mutational load; Next-generation sequencing