Genetic and clinical characteristics of Japanese patients with sporadic somatotropinoma

Matsumoto, Ryusaku; Izawa, Masako; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Inoshita, Naoko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

doi:10.1507/endocrj.ej16-0075

Cited by 24 publications

(14 citation statements)

References 29 publications

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“…Genomic DNA was extracted from peripheral blood and cultured cells using a NucleoSpin Tissue kit (MACHE-REY-NAGEL). DNA sequence analysis of patient and iPSCs was performed by PCR-directed sequence as previously described (54). DNA sequence of cells with frameshift mutation ( Figure 6A) was determined after cloning into the pCR2.1 vector with TA cloning (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells

Matsumoto

Suga

Aoi

et al. 2019

Journal of Clinical Investigation

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Section: Methodsmentioning

confidence: 99%

Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells

Matsumoto

Suga

Aoi

et al. 2019

Journal of Clinical Investigation

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“…In patients with sporadic acromegaly a missense variant has been observed (p.E308D), affecting the intracellular loop 3 of GPR101. It is relatively rare and its role in pituitary pathogenesis is unknown (13,126,135,136,137). Other missense variants have been detected in prolactinomas and corticotropinomas with unknown impact on tumorigenesis (137,138).…”

Section: Aip Mutations In Fipa and Sporadic Pituitary Adenomasmentioning

confidence: 99%

Somatic and germline mutations in the pathogenesis of pituitary adenomas

Vandeva

Daly

Pétrossians

et al. 2019

European Journal of Endocrinology

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Pituitary adenomas are frequently occurring neoplasms that produce clinically significant disease in 1:1000 of the general population. The pathogenesis of pituitary tumors is a matter of interest as it could help to improve diagnosis and treatment. Until recently, however, disruptions in relatively few genes were known to predispose to pituitary tumor formation. In the last decade, several more genes and pathways have been described. Germline pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene were found in familial or sporadic pituitary adenomas, usually with an aggressive clinical course. Cyclin-dependent kinase inhibitor 1B (CDKN1B) pathogenic variants lead to multiple endocrine neoplasia type 4 (MEN4) syndrome, in which pituitary adenomas can occur. Xq26.3 duplications involving the gene GPR101 cause X-linked acrogigantism. The pheochomocytoma and/or paraganglioma with pituitary adenoma association (3PAs) syndrome suggests that pathogenic variants in the genes of the succinate dehydrogenase complex or MYC-associated factor X (MAX) might be involved in pituitary tumorigenesis. New recurrent somatic alterations were also discovered in pituitary adenomas, such as, ubiquitin-specific protease 8 (USP8) and USP48 pathogenic variants in corticotropinomas. The aim of the present review is to provide an overview of the genetic pathophysiology of pituitary adenomas and their clinical relevance.

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“…Different clinical features arise depending on the causative genes. AIP mutations are related to juvenile onset, large tumor size, invasive tumors, and poor response to somatostatin analogs [1]. GPR101 mutations are increasingly reported and are related to early age onset.…”

Section: Discussionmentioning

confidence: 99%

“…The most frequent mutations in patients with GHomas are in GNAS, and these mutations are reported in 40% of GHomas [7]. Half of Japanese adults with GHoma have GNAS mutations [1]. We surveyed available English-language studies on GHomas or pituitary gigantism [1,[3][4][5].…”

Section: Discussionmentioning

confidence: 99%

GH/PRL-secreting pituitary macroadenoma associated with <i>GNAS</i> p.Gln227Leu mutation: pediatric case report and review

Watanabe

Yagasaki

Kojika³

et al. 2019

Endocr J

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GH-secreting pituitary adenomas (GHomas) are rare in the pediatric population. Guanine nucleotide-binding protein, alpha stimulating (GNAS) somatic mutations are often found in patients with GHoma. Here, we report an 8-year-old girl with GH-secreting pituitary adenoma successfully treated by operative tumor resection and postoperative treatment with octreotide long-acting release (LAR). Tumor DNA sequence analysis revealed a somatic heterozygous c.680A>T (p.Gln227Leu) mutation in GNAS. We reviewed 1,084 cases of GHomas, 409 (37.7%) of which harbored GNAS mutations. In pediatrics cases, aged 15 years or younger, 11 harbored a GNAS mutation, and GNAS p.Arg201Cys was identified in five cases. No other cases of codon 227 mutation were detected. These cases suggest that, in pediatric patients, the clinical features of GHoma may differ from those observed in adults. This is possibly related to octreotide or dopamine agonist resistance. Of six patients with surgical resistance, only one was reactive when treated with octreotide. Our case shows that octreotide LAR is an effective choice for treating GNAS-induced GHoma. This is the first report detailing the effectiveness of octreotide LAR in a GNAS codon 227 mutation-induced GHoma in a pediatric case. Examination of the relationship between genetic variation and clinical features in pediatric patients will enable us to assess the long-term effects of surgical and medical treatment of GHomas.

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Genetic and clinical characteristics of Japanese patients with sporadic somatotropinoma

Cited by 24 publications

References 29 publications

Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells

Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells

Somatic and germline mutations in the pathogenesis of pituitary adenomas

GH/PRL-secreting pituitary macroadenoma associated with <i>GNAS</i> p.Gln227Leu mutation: pediatric case report and review

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