Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

Detection of disruption in the PI3K/AKT pathway in patients with ileal carcinoids

Investigator: Christen J. Lennon, Columbia University College of Physicians and Surgeons

Mentors: Dario Garcia-Carracedo, PhD; Gloria Su, PhD; The Department of Otolaryngology, Columbia University College of Physicians and Surgeons

Phosphorylation of AKT and mutations within genes in the mTOR pathway, including PIK3CA and PTEN, have been observed in neuroendocrine tumors. There has been a demonstrated therapeutic benefit of mTOR inhibitors in pancreatic neuroendocrine tumors. Given the potential clinical implications of discovering perturbations in the PI3K/AKT pathway, we investigated its disruption in ileal carcinoids, a subset of gastrointestinal neuroendocrine tumors, which has not been evaluated previously. Paraffin-embedded ileal carcinoid samples and normal tissue from patients with intraductal papillary mucinous neoplasms were microdissected and DNA was isolated. Using mutant-enriched sequencing methods to detect mutations with enhanced sensitivity, we analyzed the common hotspot mutations of PIK3CA (3 hotspots) and AKT (1 hotspot) in our sample of ileal carcinoid tumors. Finally, gene amplification of PIK3CA and AKT was evaluated by quantitative analysis by real-time PCR. Our sample of paraffin-embedded tissue consisted of 84 total samples, with 51 samples taken from primary ileal carcinoid tumors in 26 patients and 33 samples taken from liver metastases of 19 patients with ileal carcinoids. There were 30 total patients in our study. There were no mutations found in the three PIK3CA hotspots nor the AKT hotspot. Quantitative PCR analysis revealed gene amplification of PIK3CA in one primary tumor, with a relative copy number of 2.77 and gene amplification of AKT1 in one primary tumor, with a relative copy number of 4.25. This study did not provide evidence for mutations in PIK3CA or AKT in ileal carcinoids, although it did suggest perturbation in the PIK3CA/AKT pathway in such tumors through gene amplification. Given the incredible clinical significance of such perturbations, other components of the pathway should be investigated in patients with ileal carcinoids in future studies.

Updated on February 6, 2013.


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