Association of prolactin receptor PRLR) variants with prolactinomas

Abstract

Prolactinomas are the most frequent type of pituitary tumors, which represent 10-20% of all intracranial neoplasms in humans. Prolactinomas develop in mice lacking the prolactin receptor PRLR), which is a member of the cytokine receptor superfamily that signals via Janus kinase-2-signal transducer and activator of transcription-5 JAK2-STAT5) or phosphoinositide 3-kinase-Akt PI3K-Akt) pathways to mediate changes in transcription, differentiation and proliferation. To elucidate the role of the PRLR gene in human prolactinomas, we determined the PRLR sequence in 50 DNA samples 35 leucocytes, 15 tumors) from 46 prolactinoma patients 59% males, 41% females). This identified six germline PRLR variants, which comprised four rare variants Gly57Ser, Glu376Gln, Arg453Trp and Asn492Ile) and two low-frequency variants Ile76Val, Ile146Leu), but no somatic variants. The rare variants, Glu376Gln and Asn492Ile, which were in complete linkage disequilibrium, and are located in the PRLR intracellular domain, occurred with significantly higher frequencies P 0.0001)