Research on brain tumors

Olivera Casar‑Borota (Uppsala), Jelena Jotanovic (Uppsala), Fredrik Pontén (Uppsala)

Pituitary neuroendocrine tumors (PitNETs) traditionally designated as pituitary adenomas are typically benign tumours with complex clinical symptoms related to hormone hypersecretion and/or growing intracranial tumor mass. Classification of PitNETs according to pituitary cell lineages based on the expression of anterior pituitary hormones and pituitary specific transcription factors is relatively new and still not validated in large studies. The new classification has questioned the existence of hormone- and transcription factors-negative tumours, previously classified as null cell adenomas. Genetic factors that influence growth and invasiveness of PitNETs are largely unknown.

In a recent study, we performed genome-wide mRNA sequencing on 51 PitNETs of different types collected through the UCAN project. The global gene expression profiles of all the tumours were compared using modern bioinformatical tools. We identified three main clusters of PitNETs that were aligned with the main pituitary transcription factors expression patterns. Although based on data from only two tumours, we provided further evidence that “null cell adenomas” probably do not exist. Moreover, our analyses enabled further identification of gene signatures with a potential role as PitNET’s drivers and growth regulators. Upregulation of known tumour suppressor genes may partly explain typically indolent clinical course in patients with PitNETs.

We have shown that the overall gene expression pattern in PitNETs is aligned with the current cell lineage based classification of PitNETs. The transcriptomic analysis revealed novel potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.

Relevant publication:

• Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis