SO29: Screening of 274 familial colorectal cancer patients using a multi-gene panel

Maren F. Hansen1, Jostein Johansen2, 3, Bente A. Talseth-Palmer4, 5, Rodney Scott4, 5, 6, Liss Anne Lavik1, 7, 5, Alexandre Xavier7, Finn Drabløs2, Wenche Sjursen1.

1 – Department of Pathology and Medical Genetics, St. Olavs University Hospital, Department of Laboratory Medicine Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim  Norway. 2 – Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim Norway. 3 – Faculty of Medicine, Norwegian University of Science and Technology, Trondheim  Norway. 4 – School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle. 5 – Centre for Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales, Australia. 6 – Hunter Area Pathology Service, Pathology North, Hunter New England Area Health, Newcastle, New South Wales, Australia. 7 – School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle

Aim

The aim of this study was to find genetic causes of the increased cancer risk for patients fulfilling Amsterdam and/or Bethesda clinical criteria, but where no pathogenic MMR mutations have been identified in their samples.

Method

Custom HaloPlex gene panel targeting 112 genes (established and candidate CRC susceptibility genes), were used to generate libraries from 274 Norwegian and Australian patient samples. Sequencing was performed on Illumina HiSeq 2500 or NextSeq 500.

Results

After in silico and manual filtering of the almost 14000 variants, less than 100 unique variants remained.  About half of these variants were found in well-known CRC susceptibility genes, whereof half were pathogenic and the other half VUS. The other half of the variants were found in genes where the association to CRC is yet to be clarified.

Conclusion

We found a clear pathogenic genetic explanation for the increased cancer risk for almost 10% of the patients. This percentage may increase if some of the identified VUS also prove to be pathogenic. This study demonstrates the power of using panel based screening, rather than testing one gene after the other by Sanger sequencing.

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