Does the prevalence of <i>gsp</i> mutations in GH‐secreting pituitary adenomas differ geographically or racially? Prevalence of <i>gsp</i> mutations in Japanese patients revisited

Yasufuku‐Takano, Junko; Takano, Koji; Morita, Koji; Takakura, Kintomo; Teramoto, Akira; Fujita, Toshiro

doi:10.1111/j.1365-2265.2005.02423.x

Cited by 28 publications

(53 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rate of the gsp mutation in our series (58.1%) is comparable to the rate reported in Caucasian patients (19)(20)(21) and in a recent series of 100 Japanese patients (53.0%) (18). In studies reported in 1993, the incidence of gsp mutations in Japanese acromegalics was low as 9.3 and 4.4% (43,44); however, re-evaluation performed 10 years later by the same authors indicated that the corrected incidence was 53.1% (45).…”

Section: Gsp Mutations and Ck Staining Patternsupporting

confidence: 72%

“…The specimens were preserved under K80 8C until RNA extraction. Total RNA contents were extracted from the adenomae tissues, and the first-strand cDNA was synthesised from 5 mg total RNA by RT-PCR after removing contaminating genomic DNA as reported previously (18). To amplify the specific G s a-subunit cDNA fragment (249 bp), including codons 201 and 227 of the Gsa gene, we designed a sense primer and an antisense primer corresponding to nucleotide sequences 562-585 (5 0 -GTGTATCAAGCAGGCTGACTATGTG-3 0 ) and 793-819 (5 0 -CAGGCGGTTGTTCTGGTT-3 0 ) respectively.…”

Section: Histological Studiesmentioning

confidence: 99%

“…It is thought to be an early event in tumourigenesis and is detected in w40-50% of sporadic GHomae (18)(19)(20)(21)(22). There have been few studies on the impact of gsp mutations on the GHoma subtypes (19,23); this mutation has been documented only in DG GHomae (19,23).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae

Bakhtiar

Hirano

Arita

et al. 2010

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective: Somatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features. Methods: The study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysed gsp mutations (constitutively activating mutations of the G s a protein that is encoded by GNAS gene). Results: The 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation. Conclusion: DP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.

show abstract

Section: Gsp Mutations and Ck Staining Patternsupporting

confidence: 72%

Section: Histological Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae

Bakhtiar

Hirano

Arita

et al. 2010

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…12,22) As a member of the G-protein coupled receptor family, GHRHR consists of seven transmembrane domains. 10) The binding of GHRH to this receptor activates adenylyl cyclase, which causes an increase in intracellular cyclic adenosine monophosphate concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…9,18) Since the change mimics the condition of continuous GHRH stimulation, these mutations could cause GH secretion and somatotroph proliferation. Patients bearing GH-secreting adenoma with gsp mutations show higher, 16) lower, 8) or similar basal levels of plasma GH 5,21,22) compared with those of acromegalic patients without gsp mutations, and the responses of GH secretion to GHRH are lower than those in patients with gsp mutation-negative GH-secreting adenomas. 4,16,22) The expression levels of GHRHR in GH-secreting pituitary adenomas may also be one of the important factors for proliferation of GH-secreting pituitary adenomas.…”

Section: Introductionmentioning

confidence: 98%

Elevation of Growth Hormone-Releasing Hormone Receptor Messenger Ribonucleic Acid Expression in Growth Hormone-Secreting Pituitary Adenoma With Gs.ALPHA. Protein Mutation

Sakai

Kim

Sanno

et al. 2008

Neurol. Med. Chir.(Tokyo)

Self Cite

View full text Add to dashboard Cite

Growth hormone-releasing hormone (GHRH) stimulates not only the synthesis and secretion of GH but also the proliferation of normal somatotrophs. The expression of GHRH receptor (GHRHR) is regulated by GHRH, both of which are known to be expressed in human GH-secreting pituitary adenoma cells. Somatic mutations in the subunit of Gsa protein (gsp), lead to the constitutive activation of adenylyl cyclase in pituitary adenomas that secrete GH. It has not been examined how gsp mutations influence GHRHR expression in GH-secreting adenomas. We therefore analyzed the expression levels of GHRHR messenger ribonucleic acid (mRNA) in GH-secreting pituitary adenomas focusing on a gsp mutation. Furthermore, we investigated the effect of GHRH on the expression of GHRHR mRNA in primary cultures of GH-secreting pituitary adenoma cells. GHRHR mRNA expression levels were significantly elevated in gsp mutation-positive GH-secreting adenomas compared with those in gsp mutation-negative ones. In primary-cultured GH-secreting adenoma cells, the increase of GH secretion in response to GHRH was shown in both gsp mutation-positive and -negative adenoma cells with a significantly higher response in the latter adenoma cells. GHRH increased GHRHR mRNA expression level in gsp mutation-negative adenoma cells while it was not influenced by GHRH in gsp mutation-positive adenoma cells. These results suggest that gsp mutations up-regulate GHRHR mRNA expression in GH-secreting pituitary adenoma cells, and that gsp mutations desensitize the adenoma cells to GHRH in terms of their GHRHR mRNA expression probably because of their saturation of GHRH signaling.

show abstract

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

et al. 2008

View full text Add to dashboard Cite

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.

show abstract

Does the prevalence of gsp mutations in GH‐secreting pituitary adenomas differ geographically or racially? Prevalence of gsp mutations in Japanese patients revisited

Cited by 28 publications

References 27 publications

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae

Elevation of Growth Hormone-Releasing Hormone Receptor Messenger Ribonucleic Acid Expression in Growth Hormone-Secreting Pituitary Adenoma With Gs.ALPHA. Protein Mutation

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

Contact Info

Product

Resources

About