Abstract 1115P
Background
NET can rise in the context of hereditary syndromes (HS) stemming from MEN1, VHL, NF1 or TSC mutations. Other genes have been suggested to play a role in NET HS.
Methods
The Genetic Counseling Unit of our institution had attended 19609 individuals from 11679 pedigrees (PG) between November 1988 and February 2021. Restrospective analysis to identify patients (pts) with NET from our in-site database was carried out. Details regarding PG and germline (GL) features were obtained. According to clinical suspicion, identified pts were classified in 5 clinically presumed HS: “Hereditary breast and ovarian cancer (HBOC)”, “Hereditary non polyposis colorectal cancer (HNPCC)”, “Von Hippel-Lindau, multiple endocrine neoplasia type 1, tuberous sclerosis and neurofibromatosis type 1 (NET HS)”, “Other HS (OTHERS)” and “Undetermined HS (UND)”. Chi-squared and Fischer test were used for comparisons.
Results
142 pts with NET were identified. Most frequent NET locations were pancreas (42 pts, 29,6%), colorectal (CRC)-appendyx (24 pts, 16,9%), small intestine (19 pts, 13,4%) and lung (16 pts, 11,3%). 58 pts (40,8%) had GL testing. Pathogenic mutations were identified in 23% of all pts (1 pt was mandatory carrier; 32 wered tested). Genes most frequently involved were BRCA1/2 (9 pts, 6,5%), MEN1 (7 pts, 5,1%) and MSH2/MSH6-MLH1/PMS2 (6 pts, 4,3%). NET locations were different depending on genes involved (p<0,0001). Clinically suspected NET HS, HBOC, HNPCC, OTHERS and UND were different in terms of genes involved (p<0,0001) but also NET location (p=0,048) (see summary in the table). Table: 1115P
| NET HS (n=23) | HBOC (n=43) | HNPCC (n=25) | OTHERS (n=14) | UND (n=34) | p-value | |
| NET site | ||||||
| Appendyx, n (%) | 3 (13%) | 1 (2%) | 3 (12%) | 1 (7%) | 3 (9%) | |
| CRC, n (%) | 3 (13%) | 1 (2%) | 4 (16%) | 2 (14%) | 3 (9%) | |
| Breast, n (%) | 0 | 7 (16%) | 0 | 0 | 2 (6%) | |
| Lung, n (%) | 1 (4%) | 2 (5%) | 3 (12%) | 2 (14%) | 8 (23,5%) | |
| Pancreas, n (%) | 8 (35%) | 17 (39,5%) | 5 (20%) | 3 (21%) | 9 (26,5%) | |
| Small intestine, n (%) | 3 (13%) | 6 (14%) | 3 (12%) | 1 (7%) | 6 (18%) | |
| Stomac, n (%) | 1 (4%) | 4 (9%) | 4 (16%) | 0 | 1 (3%) | 0,048 |
Conclusions
NET may rise in the context of HS different from those already recognised. Different NET location and association with genes related to DNA repair pathways should encourage further investigation in the field of hereditary NET.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.M. Brunet Vidal: Financial Interests, Personal, Advisory Board: AstraZeneca. J.C.C. Ruffinelli: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Other: Merck; Financial Interests, Personal, Other: Novartis. C. Santos Vivas: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Sanofi. A. Teule: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: AAA; Financial Interests, Personal, Advisory Board: Pfixer; Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.