Identification of mutant K-RAS in pituitary macroadenoma

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.

Keywords: Digital PCR; K-RAS; Liquid biopsy; Macroadenoma; Pituitary adenoma.