Tumor mutation burden in gastro-entero-pancreatic-neuroendocrine neoplasms

Sun Young Jeong; Young Suk Park; Jeeyun Lee; Jaeyeon Jang; Youngkyung Jeon; Ye Ji Jung; Daeho Choi; Joohyun Hong; Seung Tae Kim

doi:10.21037/jgo-22-1190

Tumor mutation burden in gastro-entero-pancreatic-neuroendocrine neoplasms

J Gastrointest Oncol. 2023 Aug 31;14(4):1707-1714. doi: 10.21037/jgo-22-1190. Epub 2023 Jul 10.

Authors

Sun Young Jeong^{1

2}, Young Suk Park¹, Jeeyun Lee¹, Jaeyeon Jang¹, Youngkyung Jeon¹, Ye Ji Jung¹, Daeho Choi¹, Joohyun Hong¹, Seung Tae Kim¹

Affiliations

¹ Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
² Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.

Abstract

Background: As rare tumors, there are limited treatment options for neuroendocrine neoplasms (NENs). Recently, microsatellite instability (MSI) and tumor mutation burden (TMB) have been emerging as potential biomarkers in various tumors. However, there is a lack of research on the use of these biomarkers in gastro-entero-pancreatic (GEP)-NENs.

Methods: We analyzed 31 patients diagnosed with GEP-NEN between 2013 to 2022. The TMB and MSI analyses using next-generation sequencing (NGS) were performed for all patients. The TruSightTM Oncology 500 assay from Illumina was used as the NGS panel.

Results: Out of the 31 patients analyzed, the most frequent primary origin was the pancreas (12 patients, 38.7%), followed by the stomach (4 patients, 12.9%), gallbladder (4 patients, 12.9%), rectum (7 patients, 22.6%), small bowel (2 patients, 6.5%), and bile duct (1 patient, 3.2%). Among these patients, 19 (61.3%) were diagnosed with well-differentiated neuroendocrine tumors, with grade 2 being the most common (15 patients, 48.4%), followed by grade 3 (3 patients, 9.7%) and grade 1 (1 patient, 3.2%). Neuroendocrine carcinoma was confirmed in 12 patients (38.7%). The median number of metastases was 2.0 [interquartile range (IQR), 1.0-3.0], and the liver was the most common site of metastasis (23 patients, 74.2%). The median TMB was 4.7 (IQR, 3.1-6.3) mutations/Mb, and all tumors were classified as microsatellite stability (MSS). Only one patient had a high TMB (266.4 mutations/Mb), which was a grade 3 neuroendocrine tumor originating from the pancreas. The TMB value did not vary depending on the primary tumor site or World Health Organization (WHO) grade.

Conclusions: This analysis showed that, despite very low incidence, there are GEP-NENs with high TMB. For precision medicine, testing for MSI and TMB is needed for this tumor type.

Keywords: Tumor mutation burden (TMB); gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN); neuroendocrine carcinoma (NEC); neuroendocrine tumor (NET).