P39: Somatic mutations in MUTYH-associated Polyposis (MAP)

Robert Hüneburg1,5, Peer van Heteren1,5, Tobias J Weismüller1,5, Stefan Aretz2,5, Alberto Perez Bouza3,5, Elisabeth Sievers3,5, Dimitrios Pantelis4,5, Jörg C Kalff4,5, Jacob Nattermann1,5, Christian P Strassburg1,5, Sven Perner3, Glenn Kristiansen3,5, Jutta Kirfel3,5.

1 – Department of Internal Medicine I, University Hospital Bonn. 2 – Institute of Human Genetics, University Hospital Bonn. 3 – Institute of Pathology, University Hospital Bonn. 4 – Department of Surgery, University Hospital Bonn. 5 – Center for Hereditary Tumour Syndromes, University Hospital Bonn.

Aim

The KRAS gene is analyzed in metastatic CRC to predict the response of EGFR antagonists. The c.34G>T KRAS mutation is a transversion representing 8.8% of total KRAS mutations in sporadic CRC. An increased rate of this KRAS mutation in MUTYH adenomas or adenocarcinomas has been reported. Therefore, it is hypothesized that this mutation may be useful as a pre-screening test for MAP diagnosis and additionally may serve as a tool for classifying variants of uncertain significance at MUTYH.

Method

The study retrospectively enrolled 11 patients in two different centers during 2008 till 2013. After deparaffinization, tumour tissue was macrodissected from unstained slides, genomic DNA extracted out of normal tissue and polyps followed by Sanger sequencing.

Results

A total number of 11 unrelated patients with a known biallelic MUTYH mutation were included. In 8 patients a colectomy was performed due to the high number of polyps, in 2 patients due to colorectal cancer, one patient is under endoscopic treatment. In 24/66 adenomas a KRAS mutation was detected (18x p.G12C, 4x p.G13D, 2x p.G12V), in 3/7 hyperplastic polyps a p.G12C mutation and in one colorectal carcinoma a p.G12V mutation.

Conclusion

The somatic KRAS Gly12Cys mutation has been reported with a high specificity of MUTYH. In our study we can show the same mutation in most of the adenomas. We could identify further somatic mutations which needs further validation.

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