title: Less frequently mutated genes in colorectal cancer: evidences from next-generation sequencing of 653 routine cases.
abstract: OBJECTIVE
  The incidence of RAS/RAF/PI3KA and TP53 gene mutations in colorectal cancer (CRC) is well established. Less information, however, is available on other components of the CRC genomic landscape, which are potential CRC prognostic/predictive markers.
  
  
  METHODS
  Following a previous validation study, ion-semiconductor next-generation sequencing (NGS) was employed to process 653 routine CRC samples by a multiplex PCR targeting 91 hotspot regions in 22 CRC significant genes.
  
  
  RESULTS
  A total of 796 somatic mutations in 499 (76.4%) tumours were detected. Besides RAS/RAF/PI3KA and TP53, other 12 genes showed at least one mutation including FBXW7 (6%), PTEN (2.8%), SMAD4 (2.1%), EGFR (1.2%), CTNNB1 (1.1%), AKT1 (0.9%), STK11 (0.8%), ERBB2 (0.6%), ERBB4 (0.6%), ALK (0.2%), MAP2K1 (0.2%) and NOTCH1 (0.2%).
  
  
  CONCLUSIONS
  In a routine diagnostic setting, NGS had the potential to generate robust and comprehensive genetic information also including less frequently mutated genes potentially relevant for prognostic assessments or for actionable treatments.
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Malapelle
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pisapia
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Sgariglia
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Vigliar
authors.affiliation: Department of Oncology, AORN Cardarelli, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Biglietto
authors.affiliation: Department of Surgical and Clinical Medicine, University of Naples Federico II, Naples, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Carlomagno
authors.affiliation: Department of "Patologia Umana dell'Adulto e dell'età evolutiva, G.Barresi", University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giuffrè
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Claudio
authors.identifier: http://orcid.org/0000-0002-7479-6457
authors.initials: C
authors.lastname: Bellevicine
authors.affiliation: Department of Public Health, University of Naples Federico II, Naples, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Troncone
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D018797:Cell Cycle Proteins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D066247:Receptor, ErbB-4 / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D017422:Sequence Analysis, DNA; D051901:Smad4 Protein / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D051881:Receptor, Notch1; D051901:Smad4 Protein; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D066247:Receptor, ErbB-4; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: COLON; MOLECULAR ONCOLOGY; MOLECULAR PATHOLOGY