G protein activation subunit genes in ovarian hemangioma. A systematic review

Authors

  • Dr .Gayathri Baluswamy MBBS MS OG MRCOG, Assistant Professor, Vels Medical College and Hospital, Manjankaranai, Tamilnadu, India
  • Dr. Karthik Shunmugavelu BDS, MDS OMFP, MSC London, Mfdsrcs England, Mfdsrcps Glasgow, Faculty Affiliate Rcs Ireland, Affiliate Rcs Edinburgh, Mcip, Fibms Usa, Masid Australia Assistant Professor, Department of Dentistry, PSP Medical College Hospital and Research Institute, Tambaram Kanchipuram main road, Oragadam, Panruti Kanchipuram district Tamilnadu 631604

DOI:

https://doi.org/10.51168/sjhrafrica.v5i12.2366

Keywords:

Ovarian, Hemangioma, vascular, tumor, benign, ovarian, G protein, GPCR, protein-protein, interactions

Abstract

Background

Heterotrimeric G-proteins transmit signals from G-protein-coupled receptors (GPCRs) to the cell interior, modulating physiological activities based on specific tissue targets. While the fundamental schemes of G-protein regulation and signaling are well-documented, their specific role in rare neoplasms like ovarian hemangiomas remains an emerging area of study. Ovarian hemangiomas are uncommon; most are characterized by isolated reports of peculiar clinical manifestations or morphologic features. To fully characterize the clinicopathologic correlations of ovarian hemangiomas and assess the importance of hormone receptors in their pathogenesis, researchers are increasingly investigating the G protein-activating subunit gene, particularly mutations in GNAQ. In other vascular tumors, somatic mutations in these G-protein subunits trigger constitutive activation of downstream pathways, such as MAPK/ERK, driving endothelial proliferation. Understanding these molecular drivers is essential for distinguishing these benign vascular lesions from malignant ovarian cancers and for developing targeted diagnostic markers that bridge the gap between heterotrimeric G-protein signaling and rare gynecological pathology.

 Material and Methods

Major databases such as Medline were explored through a detailed literature search, resulting in a systematic review pertaining to G protein activation subunit genes in ovarian hemangioma.

 Results

Eight original research scientific articles, dated between 2020 and 2024, about the mentioned topic were highlighted.

 Conclusions

Ovarian hemangiomas are extremely uncommon tumors that can occur at any age and are discovered by accident after surgery or autopsy. The purpose of this article is to highlight that these neoplasms should be considered in the differential diagnosis of a hemorrhagic ovarian lesion, even though they are extremely uncommon in the ovary. Receptor-G protein interactions have been the subject of extensive research for over 40 years, yielding significant insights into one of the most fundamental systems in human physiology.

References

Dahal M, Upadhyaya P, Adhikari P, Karki D, Regmi N. Ovarian hemangioma: a rare entity. Int J Reprod Contracept Obstet Gynecol. 2018 Jun 1;7(5):2490-2. https://doi.org/10.18203/2320-1770.ijrcog20182023

Nakuci D, Kola E, Horjeti E, Kola I, Shaipi B, Musa J, Guy A, Alimehmeti M. Ovarian hemangioma presented as an incidental ovarian mass: a rare case report along with literature review. Archives of Clinical and Medical Case Reports. 2020 Sep 3;4(5):760-5. https://doi.org/10.26502/acmcr.96550262

Shopov ST. A collision between cavernous-capillary hemangioma with stromal Luteinization and serous cystadenoma. Folia Medica. 2020 Dec 31;62(4):851-5. https://doi.org/10.3897/folmed.62.e51551

Koh LW, Sun YL, Koh PH, Chiu HY, Chen SY, Huang MH. Ovarian capillary hemangioma presenting as pseudo-Meigs' syndrome: a case report. Journal of Minimally Invasive Gynecology. 2007 May 1;14(3):367-9. https://doi.org/10.1016/j.jmig.2006.10.030

Akbulut M, Zekioglu O, Terek MC, Ozdemir N. Florid vascular proliferation in mature cystic teratoma of the ovary: case report and review of the literature. Tumori Journal. 2009 Jan;95(1):104-7. https://doi.org/10.1177/030089160909500119

Erdemoglu E, Kamaci M, Ozen S, Sahin HG, Kolusari A. Ovarian hemangioma with elevated CA125 and ascites mimicking ovarian cancer. European journal of gynaecological oncology. 2006 Jan 1;27(2):195-6. PMID: 16620071

Kryvenko ON, Gupta NS, Meier FA, Lee MW, Epstein JI. Anastomosing hemangioma of the genitourinary system: eight cases in the kidney and ovary with immunohistochemical and ultrastructural analysis. American journal of clinical pathology. 2011 Sep 1;136(3):450-7. https://doi.org/10.1309/AJCPJPW34QCQYTMT

Huang RS, Covinsky M, Zhang S. Bilateral ovarian capillary hemangioma with stromal luteinization and hyperandrogenism. Annals of Clinical & Laboratory Science. 2013 Sep 21;43(4):457-9. PMID: 24247806

Yamawaki T, Hirai Y, Takeshima N, Hasumi K. Ovarian hemangioma associated with concomitant stromal luteinization and ascites. Gynecologic oncology. 1996 Jun 1;61(3):438-41. https://doi.org/10.1006/gyno.1996.0170

Gücer F, Özyılmaz F, Balkanlı-Kaplan P, Mülayim N, Aydın Ö. Ovarian hemangioma presenting with hyperandrogenism and endometrial cancer: a case report. Gynecologic oncology. 2004 Sep 1;94(3):821-4. https://doi.org/10.1016/j.ygyno.2004.06.021

Nezhat F, Slomovitz BM, Saiz AD, Cohen CJ. Ovarian mucinous cystadenocarcinoma with virilization. Gynecologic oncology. 2002 Mar 1;84(3):468-72. https://doi.org/10.1006/gyno.2001.6542

Rezk A, Richards S, Castillo RP, Schlumbrecht M. Anastomosing hemangioma of the ovary mimics metastatic ovarian cancer. Gynecologic oncology reports. 2020 Nov 1;34:100647. https://doi.org/10.1016/j.gore.2020.100647

Liau JY, Tsai JH, Lan J, Chen CC, Wang YH, Lee JC, Huang HY. GNA11 joins GNAQ and GNA14 as a recurrently mutated gene in anastomosing hemangioma. Virchows Archiv. 2020 Mar;476(3):475-81. https://doi.org/10.1007/s00428-019-02673-y

Goldsmith ZG, Dhanasekaran DN. G protein regulation of MAPK networks. Oncogene. 2007 May;26(22):3122-42. https://doi.org/10.1038/sj.onc.1210407

Lim YH, Bacchiocchi A, Qiu J, Straub R, Bruckner A, Bercovitch L, Narayan D, McNiff J, Ko C, Robinson-Bostom L, Antaya R. GNA14 somatic mutation causes congenital and sporadic vascular tumors by MAPK activation. The American Journal of Human Genetics. 2016 Aug 4;99(2):443-50. https://doi.org/10.1016/j.ajhg.2016.06.010

Bean GR, Joseph NM, Folpe AL, Horvai AE, Umetsu SE. Recurrent GNA14 mutations in anastomosing haemangiomas. Histopathology. 2018 Aug 1;73(2). https://doi.org/10.1111/his.13519

Kurek KC, Pansuriya TC, Van Ruler MA, Van Den Akker B, Luks VL, Verbeke SL, Kozakewich HP, Sciot R, Lev D, Lazar AJ, Fletcher CD. R132C IDH1 mutations are found in spindle cell hemangiomas and not in other vascular tumors or malformations. The American Journal of Pathology. 2013 May 1;182(5):1494-500. https://doi.org/10.1016/j.ajpath.2013.01.012

Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK. Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma. The American Journal of Human Genetics. 2016 Apr 7;98(4):789-95. https://doi.org/10.1016/j.ajhg.2016.03.009

Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nature reviews Drug discovery. 2017 Dec;16(12):829-42. https://doi.org/10.1038/nrd.2017.178

Fredriksson R, Lagerström MC, Lundin LG, Schiöth HB. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Molecular pharmacology. 2003 Jun 1;63(6):1256-72. https://doi.org/10.1124/mol.63.6.1256

Laschet C, Dupuis N, Hanson J. The G protein-coupled receptors deorphanization landscape. Biochemical Pharmacology. 2018 Jul 1;153:62-74. https://doi.org/10.1016/j.bcp.2018.02.016

Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nature reviews Molecular cell biology. 2002 Sep 1;3(9):639-50. https://doi.org/10.1038/nrm908

Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nature Reviews Cancer. 2007 Feb;7(2):79-94. https://doi.org/10.1038/nrc2069

Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature. 2009 May 21;459(7245):356-63. https://doi.org/10.1038/nature08144

Hauser AS, Chavali S, Masuho I, Jahn LJ, Martemyanov KA, Gloriam DE, Babu MM. Pharmacogenomics of GPCR drug targets. Cell. 2018 Jan 11;172(1):41-54. https://doi.org/10.1016/j.cell.2017.11.033

Milligan G, Kostenis E. Heterotrimeric G‐proteins: a short history. British journal of pharmacology. 2006 Jan;147(S1):S46-55. https://doi.org/10.1038/sj.bjp.0706405

Howe AK. Cross-talk between calcium and protein kinase A in the regulation of cell migration. Current opinion in cell biology. 2011 Oct 1;23(5):554-61. https://doi.org/10.1016/j.ceb.2011.05.006

Mizuno N, Itoh H. Functions and regulatory mechanisms of Gq-signaling pathways. Neurosignals. 2009 Feb 12;17(1):42-54. https://doi.org/10.1159/000186689

Sadana R, Dessauer CW. Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies. Neurosignals. 2009 Oct 24;17(1):5-22. https://doi.org/10.1159/000166277

Brust TF, Conley JM, Watts VJ. Gαi/o-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later. European journal of pharmacology. 2015 Sep 15;763:223-32. https://doi.org/10.1016/j.ejphar.2015.05.014

Ross EM. Coordinating speed and amplitude in G-protein signaling. Current Biology. 2008 Sep 9;18(17):R777-83. https://doi.org/10.1016/j.cub.2008.07.035

Smrcka AV, Fisher I. G-protein βγ subunits as multi-functional scaffolds and transducers in G-protein-coupled receptor signaling. Cellular and Molecular Life Sciences. 2019 Nov;76(22):4447-59. https://doi.org/10.1007/s00018-019-03275-2

Blumer JB, Lanier SM. Activators of G protein signaling exhibit broad functionality and define a distinct core signaling triad. Molecular pharmacology. 2014 Mar 1;85(3):388-96. https://doi.org/10.1124/mol.113.090068

Baltoumas FA, Theodoropoulou MC, Hamodrakas SJ. Interactions of the α-subunits of heterotrimeric G-proteins with GPCRs, effectors and RGS proteins: a critical review and analysis of interacting surfaces, conformational shifts, structural diversity and electrostatic potentials. Journal of Structural Biology. 2013 Jun 1;182(3):209-18. https://doi.org/10.1016/j.jsb.2013.03.004

Vadas O, Dbouk HA, Shymanets A, Perisic O, Burke JE, Abi Saab WF, Khalil BD, Harteneck C, Bresnick AR, Nürnberg B, Backer JM. Molecular determinants of PI3Kγ-mediated activation downstream of G-protein-coupled receptors (GPCRs). Proceedings of the National Academy of Sciences. 2013 Nov 19;110(47):18862-7. https://doi.org/10.1073/pnas.1304801110

Klayman LM, Wedegaertner PB. Inducible inhibition of Gβγ reveals localization-dependent functions at the plasma membrane and Golgi. Journal of Biological Chemistry. 2017 Feb 3;292(5):1773-84. https://doi.org/10.1074/jbc.M116.750430

Milligan G, Ward RJ, Marsango S. GPCR homo-oligomerization. Current opinion in cell biology. 2019 Apr 1;57:40-7. https://doi.org/10.1016/j.ceb.2018.10.007

Simon MI, Strathmann MP, Gautam N. Diversity of G proteins in signal transduction. Science. 1991 May 10;252(5007):802-8. https://doi.org/10.1126/science.1902986

Gilman AG. G proteins: transducers of receptor-generated signals. Annual review of biochemistry. 1987 Jan 1;56(1):615-49. https://doi.org/10.1146/annurev.bi.56.070187.003151

Sprang SR, Chen Z, Du X. Structural basis of effector regulation and signal termination in heterotrimeric Gα proteins. Advances in protein chemistry. 2007 Jan 1;74:1-65. https://doi.org/10.1016/S0065-3233(07)74001-9

Noel JP, Hamm HE, Sigler PB. The 2.2 Å crystal structure of transducin-α complexed with GTPγS. Nature. 1993 Dec 16;366(6456):654-63. https://doi.org/10.1038/366654a0

Syrovatkina V, Alegre KO, Dey R, Huang XY. Regulation, signaling, and physiological functions of G-proteins. Journal of molecular biology. 2016 Sep 25;428(19):3850-68. https://doi.org/10.1016/j.jmb.2016.08.002

Kamato D, Thach L, Bernard R, Chan V, Zheng W, Kaur H, Brimble M, Osman N, Little PJ. Structure, function, pharmacology, and therapeutic potential of the G protein, Gα/q, 11. Frontiers in Cardiovascular Medicine. 2015 Mar 24;2:14. https://doi.org/10.3389/fcvm.2015.00014

Bean GR, Joseph NM, Gill RM, Folpe AL, Horvai AE, Umetsu SE. Recurrent GNAQ mutations in anastomosing hemangiomas. Modern Pathology. 2017 May;30(5):722-7. https://doi.org/10.1038/modpathol.2016.234

Bernhard SM, Han J, Che T. GPCR‐G protein selectivity revealed by structural pharmacology. The FEBS Journal. 2024 Jul;291(13):2784-91. doi: 10.1111/febs.17049 https://doi.org/10.1111/febs.17049

Torrence D, Antonescu CR. The genetics of vascular tumours: an update. Histopathology. 2022 Jan;80(1):19-32. doi: 10.1111/his.14458 https://doi.org/10.1111/his.14458

Chaudhary PK, Kim S. An insight into GPCR and G-proteins as cancer drivers. Cells. 2021 Nov 24;10(12):3288. https://doi.org/10.3390/cells10123288

Xue H, Lin XY. Asymptomatic ovarian hemangioma in a postmenopausal patient with elevated estrogen. Eur. J. Gynaecol. Oncol. 2018 Oct 10;39(5):2018. DOI: 10.12892/ejgo3835.2018

Ziari K, Alizadeh K. Ovarian hemangioma: a rare case report and review of the literature. Iranian journal of pathology. 2016;11(1):61. PMID: 26870145

Schoolmeester JK, Greipp PT, Keeney GL, Soslow RA. Ovarian hemangiomas do not harbor EWSR1 rearrangements: clinicopathologic characterization of 10 cases. International Journal of Gynecological Pathology. 2015 Sep 1;34(5):437-44.

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Published

2025-12-31

How to Cite

Baluswamy, D. .Gayathri ., & Shunmugavelu, D. K. . (2025). G protein activation subunit genes in ovarian hemangioma. A systematic review. Student’s Journal of Health Research Africa, 5(12), 10. https://doi.org/10.51168/sjhrafrica.v5i12.2366

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Section

Section of Endocrinology and Reproductive Health

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