A Novel Six-nucleotide Insertion in Exon 4 of the MEN1 Gene, 878insCTGCAG, in Three Patients with Familial Insulinoma and Primary Hyperparathyroidism

Okamoto, Hiroomi; Tamada, Akira; Hai, Noritaka; Doi, Masaru; Uchimura, Isao; Hirata, Yukio; Kosugi, Shinji

doi:10.1093/jjco/hyf079

Cited by 3 publications

(1 citation statement)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Okamoto et al . suggested that a novel six‐nucleotide insertion in exon 4 of the MEN1 gene might contribute to the familial insulinoma. A prior study indicated that MEN1 gene mutations were lacking in 27 sporadic insulinomas .…”

Section: Discussionmentioning

confidence: 99%

Two nonsense somatic mutations in MEN1 identified in sporadic insulinomas

et al. 2018

View full text Add to dashboard Cite

Insulinomas are functional pancreatic neuroendocrine tumors that cause hypoglycemia and severe morbidity. The aim of our study was to identify gene mutations responsible for tumorigenesis of sporadic insulinoma. Whole exome sequencing analysis was performed on tumors and paired peripheral blood from three patients with insulinomas. After initial analysis, somatic mutations were obtained and a deleterious protein product was further predicted by various bioinformatic programs. Whole exome sequencing identified 55 rare somatic mutations among three insulinoma patients, including MEN1 gene nonsense mutations (c. 681C>G; p.Tyr227* in exon 4 of MEN1 and c. 346G>T; p.Glu116* in exon 2 of MEN1 ) in two different tumor samples. The mutations resulted in a significant truncation of the protein and a non‐functional gene product, which was involved in defective binding of menin to proteins implicated in genetic and epigenetic mechanisms. Our results extend the growing list of pathogenic MEN1 mutations in sporadic cases of insulinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Two nonsense somatic mutations in MEN1 identified in sporadic insulinomas

et al. 2018

View full text Add to dashboard Cite

show abstract

Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1

Peppa

Boutati

Kamakari

et al. 2008

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

Multiple Endocrine Neoplasia Type 1 Variant with Frequent Prolactinoma and Rare Gastrinoma

Hao

Skarulis²,

Simonds³

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

View full text Add to dashboard Cite

No variant of multiple endocrine neoplasia type 1 (MEN1) has been reproducible among families. We examined two large kindreds with MEN1 variants, and we compared these to past reports. The two kindreds were followed up for 20-30 yr with MEN1 tumors in 30 members. Results in cases from two kindreds were that 93% showed parathyroid adenoma, 40% pituitary tumor (always prolactinoma), and 27% enteropancreatic endocrine tumor. The latter included 10% insulinoma, 7% nonfunctioning islet tumor, but only 10% gastrinoma. Compared with prior large series, this lower prevalence of gastrinoma (10% vs. 42%, P < 0.01) and higher prevalence of prolactinoma (40% vs. 22%, P < 0.01) define this variant. Many possible biases of retrospective analyses were excluded as possible explanations. Previously sequenced DNA showed no characteristic MEN1 mutation in these two kindreds and in a third, reported previously; the lack of any shared MEN1 mutation also excluded common ancestry for MEN1 among the three kindreds. The causes for differences between this variant and typical MEN1 are unknown. In conclusion, this variant shows more frequent prolactinoma and less frequent gastrinoma than typical MEN1; the variant is reproducible among kindreds. MEN1 carriers in such families should have periodic monitoring adjusted for the expected penetrance of tumors.

show abstract

A Novel Six-nucleotide Insertion in Exon 4 of the MEN1 Gene, 878insCTGCAG, in Three Patients with Familial Insulinoma and Primary Hyperparathyroidism

Cited by 3 publications

References 12 publications

Two nonsense somatic mutations in MEN1 identified in sporadic insulinomas

Two nonsense somatic mutations in MEN1 identified in sporadic insulinomas

Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1

Multiple Endocrine Neoplasia Type 1 Variant with Frequent Prolactinoma and Rare Gastrinoma

Contact Info

Product

Resources

About