title: Endoscopic ultrasound fine-needle aspiration cytology mutation profiling using targeted next-generation sequencing: personalized care for rectal cancer.
abstract: OBJECTIVE
  In an era of precision medicine, our aim was to determine the frequency and theranostic potential of mutations identified in malignant lymph nodes (LNs) sampled by endoscopic ultrasound fine-needle aspiration (EUS FNA) of patients with rectal cancer by targeted next-generation sequencing (NGS).
  
  
  METHODS
  The NGS Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, CA) and MiSeq (Illumina, San Diego, CA) sequencers were used to sequence and assess for 2,800 or more possible mutations in 50 established cancer-associated genes.
  
  
  RESULTS
  Among 102 patients, 89% had 194 pathogenic alterations identified in 19 genes. The identification of KRAS, NRAS, or BRAF mutations suggests that 42% are likely nonresponders to anti-epidermal growth factor receptor therapy. Among KRAS, NRAS, or BRAF wild-type patients, alterations in eight genes linked to alternative therapies were identified in 44%.
  
  
  CONCLUSIONS
  Our data demonstrate the successful ability to apply a single multiplex test to allow multigene mutation detection from malignant LN cytology specimen DNA collected by EUS FNA.
authors.affiliation: From the Divison of Gastroenterology and Hepatology, gleeson.ferga@mayo.edu.
authors.forename: Ferga C
authors.initials: FC
authors.lastname: Gleeson
authors.affiliation: Department of Anatomic Pathology.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kipp
authors.affiliation: Department of Anatomic Pathology.
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Voss
authors.affiliation: Department of Anatomic Pathology.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Campion
authors.affiliation: Department of Anatomic Pathology.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Minot
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, and.
authors.forename: Zheng J
authors.initials: ZJ
authors.lastname: Tu
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, and.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
authors.affiliation: Department of Anatomic Pathology.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Sciallis
authors.affiliation: Department of Anatomic Pathology.
authors.forename: Rondell P
authors.initials: RP
authors.lastname: Graham
authors.affiliation: From the Divison of Gastroenterology and Hepatology, Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Lazaridis
authors.affiliation: Department of Anatomic Pathology.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Henry
authors.affiliation: From the Divison of Gastroenterology and Hepatology.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Levy
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044963:Biopsy, Fine-Needle; D004252:DNA Mutational Analysis / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D057285:Precision Medicine / Q000379:methods*; D011351:Proctoscopy; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Endoscopic ultrasound fine-needle aspiration; Malignant cytology; Personalized medicine; Targeted next-generation sequencing; Theranostics