Profiling of GEPNETs

Abstract EN

The tumorigenesis of gastrointestinal and pancreatic tumors (GEPNETs) is poorly understood.

We need a better understanding of the molecular alterations in GEPNETs to obtain an accurate classification, and it may also provide targets for therapeutic intervention.

Purpose of Paper.

The purpose of this paper was to critically examine recent advances in the molecular understanding of GEPNETs gained from genome-wide and transcriptome-wide profiling studies.

Special emphasis was put on diagnostic, predictive, and therapeutic implications of profiling studies.

Results.

Pancreatic neuroendocrine tumours (PNETs) were characterised by a distinct pattern of chromosomal alterations and a higher degree of chromosomal instability (CIN) than ileal carcinoids.

Subgroups of PNETs and ileal carcinoids were identified on the basis of specific chromosomal alterations.

Exome sequencing identified mutations in MEN1, ATRX/DAXX, and mTOR pathway genes as being frequent events in sporadic PNETs.

Expression profiles of PNETs and ileal carcinoids were found to be different, and allowed identification of subgroups of tumors, as well discrimination between benign and malignant tumors.

The molecular data provided a number of candidate genes and pathways suitable for targeted therapy.

For PNETs, candidate targets include BRAF, KRAS, TERT, EGFR, RET, MDM2, IGF, MET/HGF, ANG2, LCK, PDGFRB, AKT-mTOR, and SSTR2.

Some of these targets have already been evaluated in clinical trials (mTOR and SSTR2).

For ileal carcinoids, significantly fewer candidate targets were provided, including ERBB2 (HER2), RET, APLP1, and Notch.

Conclusion.

Profiling of GEPNETs is a powerful tool for discovery of novel targets for therapeutic intervention.

Further studies, combining genome, epigenome, transcriptome, and proteome data are needed to enable us to identify clinically relevant targets in GEPNETs.