Absence of activating mutations of CXCR4 in pituitary tumours.
OBJECTIVE
Mutations of the gsp oncogene are responsible for 30-40% of GH-producing pituitary adenomas and 10% of nonfunctioning pituitary adenomas (NFPAs). However, the pathogenetic mechanism of the remaining pituitary tumours still remains to be identified. Recently, the interaction between the chemokine stromal cell-derived factor 1 and its receptor CXCR4 was found to play an important role in GH production and cell proliferation in various pituitary adenoma cell lines. As CXCR4 is a Gi-coupled chemokine receptor, its constitutive activating mutations may be involved in pituitary tumour formation by cyclic adenosine monophosphate (cAMP)-independent, ERK-related pathways.


METHODS
We investigated whether somatic activating-mutations of CXCR4 might be a possible tumourigenic mechanism for gsp-negative GH-secreting pituitary adenomas and NFPAs. Direct sequencing of polymerase chain reaction-amplified products for coding exons of CXCR4 were performed using genomic deoxyribonucleic acid samples from 37 GH-producing pituitary tumour tissues that were negative for the gsp mutation and 14 CXCR4 expressing NFPAs.


RESULTS
Immunohistochemical analyses and double immunofluorescent staining of sectioned paraffin-embedded pituitary tissues revealed that CXCR4 is highly expressed in GH-producing pituitary adenomas and NFPAs. Direct sequencing showed that two synonymous mutations in exon 2 (87 C > T and 414 C > T) were detected in 4 out of 51 pituitary tumours.


CONCLUSIONS
Our results indicate that an activating mutation of the CXCR4 may not be a common pathogenetic mechanism in GH-producing pituitary tumours and NFPAs.
Lee
Yong-ho
YH
Endocrinology, Internal Medicine, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea.
Noh
Tae Woong
TW
Lee
Mi Kyung
MK
Jameson
J Larry
JL
Lee
Eun Jig
EJ
D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism*
D019718:Receptors, CXCR4