title: Frequency of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathway pathogenic alterations in EUS-FNA sampled malignant lymph nodes in rectal cancer with theranostic potential.
abstract: BACKGROUND
  Targeted next-generation sequencing has the potential to stratify a tumor by molecular subtype and aid the development of a biomarker profile for prognostic risk stratification and theranostic potential.
  
  
  OBJECTIVE
  To assess the frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens.
  
  
  METHODS
  Multigene molecular profiling of archived malignant EUS-FNA lymph node cytology specimens using the Ion Ampliseq Cancer Hotspot Panel v2, which targets at least 2855 possible mutations within 50 cancer-associated genes.
  
  
  METHODS
  Single tertiary referral center.
  
  
  METHODS
  Sporadic, treatment naive, locally advanced primary rectal cancer by EUS-FNA (n = 76) who subsequently completed neoadjuvant therapy with on-site oncologic surgery.
  
  
  METHODS
  The frequency and distribution of pathogenic alterations in malignant lymph node cytology specimens by the mitogen-activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling pathways, by KRAS or NRAS wild-type lymph node status, by extramesenteric lymph node status, and by a complete pathologic response status.
  
  
  RESULTS
  Eleven patients (14.5%) were 50-gene panel wild-type. Sixty-five patients had 139 pathogenic alterations (2 [1-3] per patient) in 13 of 50 evaluated genes. The following represent a spectrum of identified alterations: TP53 (n = 52; 68.4%), APC (n = 36; 47.4%), KRAS (n = 22; 28.9%), FBXW7 (n = 8; 10.5%), NRAS (n = 6; 7.9%), PIK3CA (n = 4; 5.3%), SMAD4 (n = 3; 3.9%), and BRAF (n = 3; 3.9%). Pathogenic alterations were identified in the MAPK and PI3K signaling pathways in 41% and 5% of patients, respectively.
  
  
  CONCLUSIONS
  Findings were limited to a 50 cancer-associated gene analysis.
  
  
  CONCLUSIONS
  Molecular EUS lymph node assessments using cancer "hotspot" panels can identify pathogenic alteration frequency and distribution and have theranostic potential for individualized patient care.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Ferga C
authors.initials: FC
authors.lastname: Gleeson
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Kipp
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Voss
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Campion
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Minot
authors.affiliation: Division of Biomedical Statics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Zheng J
authors.initials: ZJ
authors.lastname: Tu
authors.affiliation: Division of Biomedical Statics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Rondell P
authors.initials: RP
authors.lastname: Graham
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Lazaridis
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Henry
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Levy
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D057285:Precision Medicine; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D051901:Smad4 Protein / Q000235:genetics; D000068936:Theranostic Nanomedicine; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C117307:KRAS protein, human; D008565:Membrane Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D020928:Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)