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GNA11 joins GNAQ and GNA14 as a recurrently mutated gene in anastomosing hemangioma

  • Jau-Yu Liau
  • Jia-Huei Tsai
  • Jui Lan
  • Chih-Chi Chen
  • Ying-Hao Wang
  • Jen-Chieh LeeEmail author
  • Hsuan-Ying HuangEmail author
Brief Report
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Abstract

Anastomosing hemangioma (AH) is a distinct benign vascular tumor that may be histologically confused with an angiosarcoma. Recently, recurrent GNAQ and GNA14 mutations were identified in AH. GNA11, another paralogue of GNAQ and the one that shows the highest degree of homology to GNAQ, has not yet been found to be mutated in AH. In this study, we investigated the clinicopathological and molecular features of 26 AHs. By Sanger sequencing and MassARRAY analysis, mutually exclusive mutations in exon 5 of GNAQ, GNA11, and GNA14 were identified in 10, 5, and 5 tumors, respectively, of the 22 investigated tumors, with an overall mutation rate of 91%. No notable differences in the clinicopathological features were observed between GNAQ-, GNA11-, or GNA14-mutated tumors. Our results implicated GNA11 mutations, as well as previously known mutations of its paralogues GNAQ and GNA14, as essential drivers in the pathogenesis of AH.

Keywords

Anastomosing hemangioma GNAQ GNA11 GNA14 

Notes

Acknowledgments

The authors are grateful to Dr. Yi-Jia Lin at Tri-Service General Hospital, Taipei, Taiwan and Dr. Yu-Chien Kao at Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan for contributing the two consultation cases.

Author contributions

JYL conceived the study and wrote the manuscript. JYL, JCL, and HYH reviewed the histological sections and designed the experiments. JYL, JHT, and JL analyzed the data. CCC and YHW performed the experiments.

Funding information

This work was in part supported by grants MOST 106-2320-B-002-028-MY3 from the Ministry of Science and Technology, Taiwan to Dr. Jen-Chieh Lee, 108-S4200 from National Taiwan University Hospital to Jau-Yu Liau, and Chang Gung Hospital (CMRPG8G0881) to Hsuan-Ying Huang.

Compliance with ethical standards

The data and experiments reported here were carried out in agreements with the Declaration of Helsinki principles and in agreement with the Ethics Committee of National Taiwan University Hospital.

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Montgomery E, Epstein JI (2009) Anastomosing hemangioma of the genitourinary tract: a lesion mimicking angiosarcoma. Am J Surg Pathol 33:1364–1369.  https://doi.org/10.1097/PAS.0b013e3181ad30a7 CrossRefPubMedGoogle Scholar
  2. 2.
    Lin J, Bigge J, Ulbright TM, Montgomery E (2013) Anastomosing hemangioma of the liver and gastrointestinal tract: an unusual variant histologically mimicking angiosarcoma. Am J Surg Pathol 37:1761–1765.  https://doi.org/10.1097/PAS.0b013e3182967e6c CrossRefPubMedGoogle Scholar
  3. 3.
    John I, Folpe AL (2016) Anastomosing hemangiomas arising in unusual locations: a clinicopathologic study of 17 soft tissue cases showing a predilection for the paraspinal region. Am J Surg Pathol 40:1084–1089.  https://doi.org/10.1097/PAS.0000000000000627 CrossRefPubMedGoogle Scholar
  4. 4.
    Bean GR, Joseph NM, Gill RM, Folpe AL, Horvai AE, Umetsu SE (2017) Recurrent GNAQ mutations in anastomosing hemangiomas. Mod Pathol 30:722–727.  https://doi.org/10.1038/modpathol.2016.234 CrossRefPubMedGoogle Scholar
  5. 5.
    Bean GR, Joseph NM, Folpe AL, Horvai AE, Umetsu SE (2018) Recurrent GNA14 mutations in anastomosing haemangiomas. Histopathology 73:354–357.  https://doi.org/10.1111/his.13519 CrossRefPubMedGoogle Scholar
  6. 6.
    Ayturk UM, Couto JA, Hann S, Mulliken JB, Williams KL, Huang AY, Fishman SJ, Boyd TK, Kozakewich HP, Bischoff J, Greene AK, Warman ML (2016) Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma. Am J Hum Genet 98:789–795.  https://doi.org/10.1016/j.ajhg.2016.03.009 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Liau JY, Lee JC, Tsai JH, Chen CC, Chung YC, Wang YH (2019) High frequency of GNA14, GNAQ, and GNA11 mutations in cherry hemangioma: a histopathological and molecular study of 85 cases indicating GNA14 as the most commonly mutated gene in vascular neoplasms. Mod Pathol:1–9.  https://doi.org/10.1038/s41379-019-0284-y CrossRefGoogle Scholar
  8. 8.
    Lim YH, Bacchiocchi A, Qiu J, Straub R, Bruckner A, Bercovitch L, Narayan D, Yale Center for Mendelian Genomics, McNiff J, Ko C, Robinson-Bostom L, Antaya R, Halaban R, Choate KA (2016) GNA14 somatic mutation causes congenital and sporadic vascular tumors by MAPK activation. Am J Hum Genet 99:443–450.  https://doi.org/10.1016/j.ajhg.2016.06.010 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O’Brien JM, Simpson EM, Barsh GS, Bastian BC (2009) Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 457:599–602.  https://doi.org/10.1038/nature07586 CrossRefPubMedGoogle Scholar
  10. 10.
    Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC (2010) Mutations in GNA11 in uveal melanoma. N Engl J Med 363:2191–2199.  https://doi.org/10.1056/NEJMoa1000584 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J (2013) Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 368:1971–1979.  https://doi.org/10.1056/NEJMoa1213507 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Thomas AC, Zeng Z, Rivière JB, O'Shaughnessy R, Al-Olabi L, St-Onge J, Atherton DJ, Aubert H, Bagazgoitia L, Barbarot S, Bourrat E, Chiaverini C, Chong WK, Duffourd Y, Glover M, Groesser L, Hadj-Rabia S, Hamm H, Happle R, Mushtaq I, Lacour JP, Waelchli R, Wobser M, Vabres P, Patton EE, Kinsler VA (2016) Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis. J Invest Dermatol 136:770–778.  https://doi.org/10.1016/j.jid.2015.11.027 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Joseph NM, Brunt EM, Marginean C, Nalbantoglu I, Snover DC, Thung SN, Yeh MM, Umetsu SE, Ferrell LD, Gill RM (2018) Frequent GNAQ and GNA14 mutations in hepatic small vessel neoplasm. Am J Surg Pathol 42:1201–1207.  https://doi.org/10.1097/PAS.0000000000001110 CrossRefPubMedGoogle Scholar
  14. 14.
    Le Guin CHD, Metz KA, Kreis SH, Bechrakis NE, Bornfeld N, Zeschnigk M, Lohmann DR (2019) Cancers (Basel) 11:1031.  https://doi.org/10.3390/cancers11071031 CrossRefGoogle Scholar
  15. 15.
    Groesser L, Peterhof E, Evert M, Landthaler M, Berneburg M, Hafner C (2016) BRAF and RAS mutations in sporadic and secondary pyogenic granuloma. J Invest Dermatol 136:481–486.  https://doi.org/10.1038/JID.2015.376 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PathologyNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiTaiwan
  2. 2.Graduate Institute of PathologyNational Taiwan University College of MedicineTaipeiTaiwan
  3. 3.Department of Anatomic PathologyKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiungTaiwan

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