Endocrinol Metab (Seoul). 2024;39(6):956-964.

Genetic Landscape and Clinical Manifestations of Multiple Endocrine Neoplasia Type 1 in a Korean Cohort: A Multicenter Retrospective Analysis.

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제1저자 김보람, 이승훈 · 교신저자 성문우, 김정희

PMID 39552147 PMC11695471 DOI 10.3803/EnM.2024.2008 IF 5.1 내분비대사내과

소속 (10)

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGRUOUND Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants.

METHODS This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines.

RESULTS A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040).

CONCLUSION The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Keywords

GenotypeKoreaMulticenterMultiple endocrine neoplasiaMultiple endocrine neoplasia type 1PhenotypeVariant

Figures

**Fig. 1.** Prevalence of the primary hyperparathyroidism, gastroenteropancreatic and pituitary neuroendocrine tumor triad among (A) the total multiple endocrine neoplasia type 1 (MEN1) cohort (n=117) and (B) the index cases (n=84).

**Fig. 2.** Distribution of multiple endocrine neoplasia type 1 (*MEN1*) variants in the study cohort. The number of patients with each variant is indicated by the number within each circle, as well as circle size. Red, frameshift; orange, nonsense; green, in frame deletion; blue, missense; purple, canonical splice site; pink, intronic; gray, large deletion.

**Fig. 3.** Frequency of the types of multiple endocrine neoplasia type 1 (*MEN1*) variants in the study cohort (n=61).

그림 출처: PubMed Central 공개 논문 (PMC11695471)

Conflict of interest statement

CONFLICTS OF INTEREST . Jung Hee Kim is a deputy editor of the journal. But she was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

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