Veronica Aran1, Manoela Heringer2, Paulo Jose da Mata3, Leandro Kasuki4,5, Renan Lyra Miranda6, Felipe Andreiuolo6, Leila Chimelli6, Paulo Niemeyer Filho3, Monica Roberto Gadelha4,5, Vivaldo Moura Neto2. 1. Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer, Rua do Rezende156-Centro, Rio de Janeiro, 20231-092, Brazil. varanponte@gmail.com. 2. Laboratório de Biomedicina do Cérebro, Instituto Estadual do Cérebro Paulo Niemeyer, Rua do Rezende156-Centro, Rio de Janeiro, 20231-092, Brazil. 3. Neurosurgery Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. 4. Neuroendocrine Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. 5. Endocrine Unit and Neuroendocrinology Research Center, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 6. Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
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.
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.
Authors: Adrian F Daly; Martine Rixhon; Christelle Adam; Anastasia Dempegioti; Maria A Tichomirowa; Albert Beckers Journal: J Clin Endocrinol Metab Date: 2006-09-12 Impact factor: 5.958
Authors: Veronica Aran; Pedro Masson Domingues; Fabiane Carvalho de Macedo; Carlos Augusto Moreira de Sousa; Tatiane Caldas Montella; Maria Theresa de Souza Accioly; Carlos Gil Ferreira Journal: Lung Cancer Date: 2017-12-11 Impact factor: 5.705
Authors: Carlos Gil Ferreira; Veronica Aran; Ilana Zalcberg-Renault; Ana Paula Victorino; Jonas H Salem; Martin H Bonamino; Fernando M Vieira; Mariano Zalis Journal: BMC Gastroenterol Date: 2014-04-10 Impact factor: 3.067