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Identification of mutant K-RAS in pituitary macroadenoma

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Abstract

Purpose

RAS genes are among the most frequently mutated genes in cancer, where their mutation frequency varies according to the distinct RAS isoforms and tumour types. Despite occurring more prevalent in malignant tumours, RAS mutations were also observed in few benign tumours. Pituitary adenomas are examples of benign tumours which vary in size and aggressiveness. The present study was performed to investigate, via liquid biopsy and tissue analysis, the presence of K-RAS mutations in a pituitary macroadenoma.

Methods

Molecular analysis was performed to investigate K-RAS mutations using the droplet digital PCR (ddPCR) method by evaluating both plasma (liquid biopsy) and the solid tumour of a patient diagnosed with a giant clinically non-functioning pituitary tumour.

Results

The patient underwent surgical resection due to visual loss, and the histopathological analysis showed a gonadotrophic pituitary macroadenoma. The molecular analysis revealed the presence of mutant K-RAS both in the plasma and in the tumour tissue which, to our knowledge, has not been previously reported in the literature.

Conclusion

Our findings highlight the exceptional capacity of the digital PCR in detecting low frequency mutations (below 1%), since we detected, for the first time, K-RAS mutations in pituitary macroadenoma. The potential impact of K-RAS mutations in these tumours should be further investigated.

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Acknowledgements

We thank the funding agencies (CNPq and FAPERJ), the patient and the Associação Mahatma Gandhi for their support.

Funding

This study was funded by the Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq Universal 427912/2018–0) and Fundação de Amparo à Pesquisa do Rio de Janeiro (FAPERJ 25191).

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Authors and Affiliations

  1. Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer, Rua do Rezende156-Centro, Rio de Janeiro, 20231-092, Brazil

    Veronica Aran, Manoela Heringer & Vivaldo Moura Neto

  2. Neurosurgery Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

    Paulo Jose da Mata & Paulo Niemeyer Filho

  3. Neuroendocrine Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

    Leandro Kasuki & Monica Roberto Gadelha

  4. Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil

    Renan Lyra Miranda, Felipe Andreiuolo & Leila Chimelli

  5. Endocrine Unit and Neuroendocrinology Research Center, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Leandro Kasuki & Monica Roberto Gadelha

Authors
  1. Veronica Aran
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  2. Manoela Heringer
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  3. Paulo Jose da Mata
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  4. Leandro Kasuki
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  8. Paulo Niemeyer Filho
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  10. Vivaldo Moura Neto
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Contributions

VA and VMN contributed to the study conception and design. Material preparation, data collection and analysis were performed by VA, MH, PJM, LK, RLM, FA, LC, MRG, VMN. The first draft of the manuscript was written by VA and VMN, and all authors contributed to the final draft. MRG and PNF critically revised the manuscript. All authors have read and approved its final draft for publication.

Corresponding author

Correspondence to Veronica Aran.

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Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Instituto Estadual do Cérebro Paulo Niemeyer (Approval number: CAAE:90680218.6.1001.8110).

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Aran, V., Heringer, M., da Mata, P.J. et al. Identification of mutant K-RAS in pituitary macroadenoma. Pituitary 24, 746–753 (2021). https://doi.org/10.1007/s11102-021-01151-6

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  • DOI: https://doi.org/10.1007/s11102-021-01151-6

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