title: Exome sequencing in one family with gastric- and rectal cancer.
abstract: BACKGROUND
  Heritable factors are well known to increase the risk of cancer in families. Known susceptibility genes account for a small proportion of all colorectal cancer cases. The aim of this study was to identify the genetic background in a family suggested to segregate a dominant cancer syndrome with a high risk of rectal- and gastric cancer. We performed whole exome sequencing in three family members, 2 with rectal cancer and 1 with gastric cancer and followed it up in additional family members, other patients and controls.
  
  
  RESULTS
  We identified 12 novel non-synonymous single nucleotide variants, which were shared among 5 affected members of this family. The mutations were found in 12 different genes; DZIP1L, PCOLCE2, IGSF10, SUCNR1, OR13C8, EPB41L4B, SEC16A, NOTCH1, TAS2R7, SF3A1, GAL3ST1, and TRIOBP. None of the mutations was suggested as a high penetrant mutation. It was not possible to completely rule out any of the mutations as contributing to disease, although seven were more unlikely than the others. Neither did we rule out the effect of all thousands of intronic, intergenic and synonymous variants shared between the three persons used for exome sequencing.
  
  
  CONCLUSIONS
  We propose this family, suggested to segregate dominant disease, could be an example of complex inheritance.
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden. jessada.thutkawkorapin@ki.se.
authors.forename: Jessada
authors.initials: J
authors.lastname: Thutkawkorapin
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden. simone.picelli@ki.se.|Eukaryotic Single Cell Genomics facility, Science for Life Laboratory, Stockholm, Sweden. simone.picelli@ki.se.
authors.forename: Simone
authors.initials: S
authors.lastname: Picelli
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden. ksvinaykumar@gmail.com.
authors.forename: Vinaykumar
authors.initials: V
authors.lastname: Kontham
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden. Tao.Liu@ki.se.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden. Daniel.Nilsson@ki.se.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nilsson
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden. Annika.Lindblom@ki.se.
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
mesh_terms: D000328:Adult; D059472:Exome; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012004:Rectal Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*