Dados do Trabalho

Título

IDENTIFICATION OF MUTANT K-RAS IN PITUITARY MACROADENOMA

Introdução

Mammalian cells differently express the RAS isoforms H-RAS, N-RAS, K-RAS, which are important in promoting oncogenic processes when mutated. RAS genes are among the most frequently affected 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, and where K-RAS mutations were not previously described. There are different methodologies employed to identify mutations including Sanger sequencing, Next Generation Sequencing (NGS) and the recent digital PCR. The advent of the non-invasive liquid biopsy took advantage of both NGS and digital PCR to detect mutations in the cancer patients’ blood, thus contributing to the field of precise and personalised medicine.

Objetivo

The present study was performed to investigate, via liquid biopsy and tissue analysis, the presence of K-RAS mutations in a pituitary macroadenoma.

Método

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.

Resultado

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 (at a frequency rate below 1%) which, to our knowledge, has not been previously reported in the literature.

Conclusão

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.

Palavras-chave

K-RAS; Liquid biopsy; Pituitary macroadenoma