title: Use of multigene-panel identifies pathogenic variants in several CRC-predisposing genes in patients previously tested for Lynch Syndrome.
abstract: BACKGROUND
  Many families with a high burden of colorectal cancer fulfil the clinical criteria for Lynch Syndrome. However, in about half of these families, no germline mutation in the mismatch repair genes known to be associated with this disease can be identified. The aim of this study was to find the genetic cause for the increased colorectal cancer risk in these unsolved cases.
  
  
  METHODS
  To reach the aim, we designed a gene panel targeting 112 previously known or candidate colorectal cancer susceptibility genes to screen 274 patient samples for mutations. Mutations were validated by Sanger sequencing and, where possible, segregation analysis was performed.
  
  
  RESULTS
  We identified 73 interesting variants, of whom 17 were pathogenic and 19 were variants of unknown clinical significance in well-established cancer susceptibility genes. In addition, 37 potentially pathogenic variants in candidate colorectal cancer susceptibility genes were detected.
  
  
  CONCLUSIONS
  In conclusion, we found a promising DNA variant in more than 25 % of the patients, which shows that gene panel testing is a more effective method to identify germline variants in CRC patients compared to a single gene approach.
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Maren F
authors.identifier: http://orcid.org/0000-0001-5231-4034
authors.initials: MF
authors.lastname: Hansen
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Jostein
authors.initials: J
authors.lastname: Johansen
authors.affiliation: Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Sylvander
authors.affiliation: Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Inga
authors.initials: I
authors.lastname: Bjørnevoll
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|School of Biomedical Science and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.|Clinic for Medicine, Møre and Romsdal Hospital Trust, Molde, Norway.
authors.forename: Bente A
authors.initials: BA
authors.lastname: Talseth-Palmer
authors.affiliation: Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Liss A S
authors.initials: LAS
authors.lastname: Lavik
authors.affiliation: School of Biomedical Science and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Xavier
authors.affiliation: Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Lars F
authors.initials: LF
authors.lastname: Engebretsen
authors.affiliation: School of Biomedical Science and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.|Division of Molecular Medicine Pathology North, NSW Pathology, Newcastle, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Finn
authors.initials: F
authors.lastname: Drabløs
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway.
authors.forename: Wenche
authors.identifier: http://orcid.org/0000-0003-3880-6440
authors.initials: W
authors.lastname: Sjursen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: Lynch syndrome; colorectal cancer; diagnostics; gene panel testing; inherited cancer; next generation sequencing (NGS)