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PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas

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Abstract

Background and aims

Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-α (PIK3CA) gene in various human tumors. Three hot-spot mutations in the exons 9 and 20 have been proven to activate the Akt signalling pathway. The Raf/MEK/ERK (mitogen-activated protein kinase) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Here we evaluate the mutational status of PIK3CA, KRAS, and BRAF in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMNC) of the pancreas.

Materials and methods

Exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 of PIK3CA, exons 1 of KRAS, and exons 5, 11, and 15 of BRAF were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing.

Results

We identified four somatic missense mutations of PIK3CA within the 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported to be a hot-spot mutation. Furthermore, we found 17 (47%) KRAS mutations in exon 1 and one missense mutation (2.7%) in exon 15 of BRAF.

Conclusion

This data is the first report of PIK3CA mutation in pancreatic cancer and it appears to be the first oncogene to be mutated in IPMN/IPMC but not in conventional ductal adenocarcinoma of the pancreas. Our data provide evidence that PIK3CA and BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.

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Authors and Affiliations

  1. Department of General Surgery, Friedrich-Alexander-University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Frank Schönleben & Werner Hohenberger

  2. Department of Otolaryngology/Head and Neck Surgery, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Frank Schönleben, Wanglong Qiu & Gloria H. Su

  3. Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Helen E. Remotti & Gloria H. Su

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  1. Frank Schönleben
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Correspondence to Frank Schönleben.

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German Society of Surgery, Surgical Forum 2008, Best Abstracts

This work was supported by the National Cancer Institute (NCI) Temin Award CA95434 and the NCI R01 CA109525 (GHS).

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Schönleben, F., Qiu, W., Remotti, H.E. et al. PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/C) of the pancreas. Langenbecks Arch Surg 393, 289–296 (2008). https://doi.org/10.1007/s00423-008-0285-7

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