Back

Integrated genomic analysis of small intestinal neuroendocrine tumors provides further insights into molecular subgroups and identifies putative driver genes

Backman, S.; Barazeghi, E.; Norlen, O.; Hellman, P.; Stalberg, P.

2025-03-12 oncology
10.1101/2025.03.10.25323484 medRxiv
Show abstract

Small intestinal neuroendocrine tumors (SI-NETs) are the most common tumor of the small intestine. Despite typically being metastatic at the time of diagnosis, the tumors are usually indolent and associated with a relatively long survival. Nevertheless, some patients fare worse and succumb to the disease soon after diagnosis despite similar stage and grade. To date, molecular prognostic markers are lacking, and our understanding of the disease biology is incomplete. Only CDKN1B is recurrently mutated in a subset of cases. Copy number alterations, including loss of chromosome 18, are common. However, the oncogenic mediators of these alterations remain unknown. The aim of this study was to identify molecular derangements in SI-NETs and identify potential prognostic markers. Forty tumor samples (including ten paired metastatic and primary tumors) from thirty patients with unusually long or unusually short survival after diagnosis were included for whole genome sequencing. Twenty of the samples were also included for RNA Sequencing. We validate known gene mutations and copy number alterations, as well as previously described molecular subgroups. We identify potential prognostic markers based on gene expression. Finally, we identify genes whose expression is affected by the most common copy number alterations in these tumors.

Matching journals

The top 8 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.