Endocrine Abstracts

Introduction: Neuroendocrine tumors (NET) arise from tissue mucosal cells known as enterochromaffin cells. The clinical behavior of NET has been recognized over the past 30 years and genome analysis are needed for further follow up. Here we conduct integrated genome analyses on data from chromosomal gene copy number and transcriptome sequencing as well as analysis of overal survival of patients diagnosed with NET.

Material and methods: The study accrued 65 patients with NET over a period of 2 years, from 2015 to 2017. During the study period, 36 patients were diagnosed with early and advanced neuroendocrine tumors oft the lung (NETL) and 29 neuroendocrine tumors of the gastroenteropancreatic system (GEP-NET). Tumor-DNA were isolated from fresh-frozen tumour tissue. Whole-genome sequencing was performed using a read length of 2×100 bp. Survival analysis oft the subjects was performed using Kaplan–Meier and Cox regression methods.

Results: Although no significant focal copy number alterations were observed across the tumours analysed, we have detected a copy number pattern compatible with chromothripsis in a sample of carcinoid and pancreatic neuroendocrine tumors. The genomic aterations found in those samples were restricted to chromosomes 3 and 13, and led to the expression of several chimeric transcripts. Wide range of mutations (n=346) were identified in chromatin-remodelling genes such as MEN1 and ARID1A. Overal survival was generally good in both groop of subjects, especially in patients with early stage disease (T1-2N0M0: 2-year survival rates of between 88% and 96%). We have not found any relations between gene profile of MEN1 and ARID1A genes and overal survival in both groups of patients.

Conclusion: The overal prognosis of NETL and GEP-NET is much better than the other primary thoracic and abdominal malignancies and is strictly related to tumor classification and TNM stage. We propose a furter gene studies to identify and then confirm genetic predictors of survival in key molecular signaling pathways among patinets with NET. This raises exciting possibilities for treating this disease in the future.