Low prevalence of Gs α mutations in śomatotroph adenomas of children and adolescents

Metzler, Markus; Luedecke, Dieter K.; Saeger, Wolfgang; Grueters, Annette; Haberl, Hannes; Kieß, Wieland; Repp, Reinald; Rascher, Wolfgang; Doetsch, Joerg

doi:10.1016/j.cancergencyto.2005.11.001

Cited by 12 publications

(9 citation statements)

References 38 publications

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“…On the other hand, although it is tempting to blame the small number of patients included in our series for such a low prevalence, the majority of the other studies included \50 patients [7, 8, 11-13, 15, 17, 19] and found prevalences around 40%. Additionally, the prevalence found in our study population is similar to that described by a few other groups besides the early Japanese studies [18,22,24]. Still, a larger series of Brazilian acromegalic patients should be evaluated for the presence of gsp mutations in order to clarify this topic.…”

Section: Discussionsupporting

confidence: 86%

“…Regarding the somatotropinomas, the prevalence of gsp we found is lower than the expected 40%, considering previous series from several countries in the literature [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The reason for such a low prevalence in our series is unknown.…”

Section: Discussioncontrasting

confidence: 81%

“…The results of these studies are summarized in Table 1. In the majority of the series, approximately 40% of the patients present a mutation [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Only four studies assessed the prevalence of the gsp oncogene in NFPA which is around ten percent [5,6,18,20].…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience

et al. 2008

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The purpose of the present study is to evaluate the prevalence of the gsp oncogene in Brazilian patients harboring somatotropinomas and non-functioning pituitary adenomas (NFPA). Patients and methods Deoxyribonucleic acid was extracted from 54 somatotropinomas and 14 NFPA. Exons 8 and 9 (including codons 201 and 227, respectively) of the GNAS gene were amplified by polymerase chain reaction (PCR). The PCR products were then purified and sequenced using the same primers. Results The gsp oncogene was found in nine tumors (eight somatotropinomas). The prevalence among somatotropinomas was 15% and among NFPA was 7%. The mutation was found in codon 201 in eight tumors and in codon 227 in one tumor (a somatotropinoma). No differences were found in age, sex, GH, and IGF-I levels or tumor volume at diagnosis between gsp+ and gsp- patients. Conclusion We found a lower than expected prevalence of gsp mutations in somatotropinomas and a similar prevalence in NFPA compared to previous studies from other countries.

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Section: Discussionsupporting

confidence: 86%

Section: Discussioncontrasting

confidence: 81%

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Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience

et al. 2008

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“…A previous study indicated that a cyclic adenosine monophosphate (cAMP) response element (CRE) located at the MEG3 proximal promoter region was critically important for promoter activity (15,16). Furthermore, gsp oncogene could increase intracellular cAMP levels and promote the phosphorylation of cyclic adenosine monophosphate-responsive element binding (p-CREB) protein, which consequently may result in the constitutive GH hypersecretion (17,18). To investigate the mechanism of gsp oncogene underlying different biochemical and clinical features of GH-secreting pituitary tumors, we hypothesized in the present study that MEG3 may serve a major role in gsp-positive tumors, as it could increase GH levels and reduce tumor volume, compared with gsp-negative tumors.…”

Section: Introductionmentioning

confidence: 99%

MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH‑secreting adenomas

et al. 2019

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Overactivation of the Gs-mediated pathway by mutations of the G-protein α subunit (Gsα), a gsp oncogene, results in increased growth hormone (GH) hypersecretion and reduced tumor volume in patients with GH-secreting pituitary tumors. However, the mechanism underlying the clinical characteristics of gsp oncogene requires further investigation. Cyclic adenosine monophosphate-responsive element binding (CREB), as a downstream target gene of gsp oncogene, is implicated in activating maternally expressed gene 3 (MEG3). The present study proposes that gsp oncogene mediates MEG3-regulating GH hypersecretion, resulting in the small tumor size of GH-secreting tumors. Therefore, the present study detected Gsα mutations by polymerase chain reaction in GH-secreting tumors, and revealed that Gsα mutations were observed in 7/25 (28%) GH-secreting tumors. Gsp-positive tumors indicated significantly increased levels of phosphorylated p-CREB (P<0.0001) and MEG3 (P=0.039), compared with gsp-negative tumors. The results indicated that MEG3 levels were positively correlated with GH and IGF-1 levels, and negatively correlated with the tumor volume of GH-secreting tumors. The group with gsp-positive or with high MEG3 expression indicated a significantly reduced proportion of invasiveness and lower Ki-67 index, compared with the gsp-negative or low MEG3 expression group. In conclusion, gsp oncogene may mediate MEG3 by promoting GH hypersecretion, resulting in smaller tumors, as well as suppressing proliferation and invasiveness of GH-secreting pituitary tumors.

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“…Depending on the cohort studied, 4.4–55% of sporadic somatotropinomas have been shown to have an activating mutation of the G protein α-subunit gene (GNAS) , known as the gsp oncogene [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. The gsp oncogene arises due to a heterozygous point mutation in the GNAS gene at codon 201 (exon 8), or less frequently at codon 227 (exon 9) [21].…”

Section: Introductionmentioning

confidence: 99%

Impact of <i>gsp</i> Oncogene on the mRNA Content for Somatostatin and Dopamine Receptors in Human Somatotropinomas

et al. 2010

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Introduction: It has been reported in some series that gsp+ somatotropinomas are more sensitive to somatostatin analogues (SA) and dopamine’s actions which may be related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile. No previous studies have been undertaken to evaluate the SSTR and DR profile related with the gsp status in somatotropinomas. Objectives: To determine if (1) gsp status is correlated with response to octreotide LAR (LAR) and tumor expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate SSTR and DR mRNA levels. Methods: Response to SA was evaluated by GH and IGF-I percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was used to determine SSTR and DR tumor expression. Primary pituitary cell cultures of primates were used to study whether SSTR and DR expression is regulated by forskolin. Results: The response to LAR did not significantly differ between patients with gsp+ and gsp– tumors; however, gsp+ tumors expressed higher levels of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1, SSTR2, DR1 and DR2 expression in cell cultures. Conclusion: Elevated SSTR1, SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA therapy; however, this study may not have been appropriately powered to observe significant effects in the clinical response. Elevated cAMP levels could be directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels observed in gsp+ patients.

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Low prevalence of Gs α mutations in śomatotroph adenomas of children and adolescents

Cited by 12 publications

References 38 publications

Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience

Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience

MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH‑secreting adenomas

Impact of <i>gsp</i> Oncogene on the mRNA Content for Somatostatin and Dopamine Receptors in Human Somatotropinomas

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