title: KRAS insertions in colorectal cancer: what do we know about unusual KRAS mutations?
abstract: BACKGROUND
  KRAS mutations are negative predictors of the response to anti-EGFR therapy in colorectal carcinomas (CRCs). Point mutations in codons 12, 13, and 61 are the most common KRAS mutations in CRC. There are few reports on insertions in KRAS, and little is known about its ability to activate the RAS pathway. The scarcity of data regarding insertion frequencies and nucleotide additions in KRAS impedes the management of patients with such mutations. We present data on KRAS insertions in CRC and discuss a case.
  
  
  METHODS
  Pyrosequencing and Sanger sequencing were performed to identify KRAS and BRAF mutations in paraffin-embedded samples of CRC. Expression of mismatch repair proteins was examined by immunohistochemistry.
  
  
  RESULTS
  We detected a GGT insertion between codons 12 and 13 (c.36_37insGGT;p.G12_G13insG) in a CRC patient. We found that insertions in KRAS is very rare in CRC and that the most frequent type of insertion is c.36_37insGGT.
  
  
  CONCLUSIONS
  KRAS gene insertions represent a diagnostic and clinical challenge due to the difficult and unusual pyrosequencing findings and the lack of information regarding its clinical impact.
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil. Electronic address: maripetaccia@gmail.com.
authors.forename: Mariana Petaccia
authors.initials: MP
authors.lastname: de Macedo
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Luiz Guilherme Cernaglia Aureliano
authors.initials: LG
authors.lastname: de Lima
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Maria Dirlei Ferreira de Souza
authors.initials: MD
authors.lastname: Begnami
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fernanda Machado
authors.initials: FM
authors.lastname: de Melo
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Louise D Brot
authors.initials: LD
authors.lastname: Andrade
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Bianca Cristina Garcia
authors.initials: BC
authors.lastname: Lisboa
authors.affiliation: Veterinary Medicine School, UNESP, Botucatu, Brazil.
authors.forename: Luisa Martelli
authors.initials: LM
authors.lastname: Soares
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE, Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Department of Molecular Diagnosis, Anatomic Pathology Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Isabela Werneck
authors.initials: IW
authors.lastname: da Cunha
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Colorectal cancer; Genetics; KRAS mutation; Molecular pathology