Germline mutation spectrum of neuroendocrine tumors (A24)

Introduction: Neuroendocrine tumors (NETs) are rare and highly heterogeneous tumors. Some specific hereditary syndromes enhance the incidence of NETs, suggesting that germline variation may
contribute to neuroendocrine tumorigenesis. However, germline genetic variants in Chinese NET
patients remain unclear.

Aim(s): To investigate the germline genetic landscape of Chinese patients with NETs.

Materials and methods: This study included histologically confirmed NET patients treated at our center from 2020 to 2023. Germline DNA extracted from saliva or blood samples was analyzed using next-generation sequencing and targeted sequencing.

Results: Of 225 Chinese NET patients, 59 (26.2%) cases had germline mutations. Among them, pancreas (27.1%, 16/59), mediastinum (27.1%, 16/59) and intestine (22.0%, 13/59) were the top 3 primary tumor locations. 32/59 (54.2%) germline variants were classified as pathogenic or likely pathogenic, while the remaining 27 (45.8%) individuals had variations of uncertain significance. The most common pathogenic/likely pathogenic mutated gene was MEN1, accounting for 4.0% (9/225) of the total, followed by PALB2 (1.3%, 3/225), VHL (0.9%, 2/225), RAD50 (0.9%, 2/225), SDHB (0.9%, 2/225) and other infrequent genes (such as CHEK2, MUTYH, RET etc.).

Conclusion: Approximately one-fourth of NET patients have germline mutation. We present
the germline mutation spectrum of neuroendocrine tumors in the Chinese population.

Keywords: germline mutation, neuroendocrine tumor, genetic