title: Yield and Clinical Utility of Next-Generation Sequencing in Selected Patients With Lung Adenocarcinoma.
abstract: Next-generation sequencing is available for assessing genomic alterations in non-small-cell lung cancer (NSCLC), although the performance characteristics and clinical utility has not been well characterized. This technique can be used to sequence hundreds of known cancer-associated genes. Our aim was to investigate the diagnostic success and clinically relevant results of extensive sequencing in NSCLC patients.
  
  
  
  A case series of 49 NSCLC patients was used to determine the success of extended next-generation sequencing, record genomic alterations, and evaluate clinical utility. Data were collected in a retrospective review. Sequencing was performed using a hybridization capture of 3320 exons from 236 cancer-related genes and 47 introns of 19 genes applied to ≥50 ng of DNA and sequenced to high, uniform coverage of 622 times.
  
  
  
  Sequencing was successful in 29 of 32 (91%) surgical/excisional specimens, and 12 of 17 (71%) nonsurgical specimens including an endoscopic forceps biopsy, core needle biopsies, fine-needle aspirates, and effusion cytologies. All 5 transthoracic core needle biopsies failed. A total of 179 genomic alterations (average 4.37 per tumor) were found. A total of 63 were clinically relevant (average 1.54 per tumor). The most frequently mutated genes were tumor protein p53, cyclin-dependent kinase inhibitor 2A, megalencephalic leukoencephalopathy with subcortical cysts 1, rapamycin-insensitive companion of mammalian target of rapamycin, epithelial growth factor receptor, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4, cyclin-dependent kinase inhibitor 2B, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α, Kirsten rat sarcoma viral oncogene homolog, Erb-B2 receptor tyrosine kinase 2, Serine/Threonine Kinase 11, and NK2 Homeobox 1. Sequencing results led to a change in management in 7 of 49 cases (14.3%).
  
  
  
  Extended next-generation sequencing was performed successfully in 41 (83.7%) cases of NSCLC using a range of pathology specimens. Testing had the potential to affect treatment decisions in selected patients.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY. Electronic address: dd2714@cumc.columbia.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: DiBardino
authors.affiliation: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Anjali
authors.initials: A
authors.lastname: Saqi
authors.affiliation: Foundation Medicine Inc, Cambridge, MA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Elvin
authors.affiliation: Foundation Medicine Inc, Cambridge, MA.
authors.forename: Joel
authors.initials: J
authors.lastname: Greenbowe
authors.affiliation: Foundation Medicine Inc, Cambridge, MA.
authors.forename: James H
authors.initials: JH
authors.lastname: Suh
authors.affiliation: Foundation Medicine Inc, Cambridge, MA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine Inc, Cambridge, MA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Division of Hematology/Oncology, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Mark
authors.initials: M
authors.lastname: Stoopler
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: William A
authors.initials: WA
authors.lastname: Bulman
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000706:statistics & numerical data*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: Cytology; Molecular analysis; Next generation sequencing; Non–small-cell lung cancer; Targeted therapy