High-mobility group A2 gene expression is frequently induced in non-functioning pituitary adenomas (NFPAs), even in the absence of chromosome 12 polysomy
Articolo
Data di Pubblicazione:
2005
Citazione:
High-mobility group A2 gene expression is frequently induced in non-functioning pituitary adenomas (NFPAs), even in the absence of chromosome 12 polysomy / G. M. Pierantoni, P. Finelli, E. Valtorta, D. Giardino, O. Rodeschini, F. Esposito, M. Losa, A. Fusco, L. Larizza. - In: ENDOCRINE-RELATED CANCER. - ISSN 1351-0088. - 12:4(2005), pp. 867-874.
Abstract:
The high-mobility group A2 (HMGA2) gene has a critical role in benign tumors where it is frequently
rearranged, and in malignant tumors, where it is overexpressed in the absence of structural
modification of the HMGA2 locus. By previous fluorescence in situ hybridization (FISH) and reverse
transcriptase PCR analyses on human prolactin-secreting pituitary adenomas we detected
rearrangement of the HMGA2 gene and amplification of its native region associated with activated
expression. These data indicated a role for the HMGA2 gene in the development of human pituitary
prolactinomas, since they are consistent with the appearance of prolactin/growth hormone
adenomas in transgenic mice overexpressing the HMGA2 gene. To assess a more general role
for HMGA2 in pituitary oncogenesis, we investigated HMGA2 amplification and expression in a
panel of non-functioning pituitary adenomas (NFPAs) which account for 25% of all pituitary
adenomas. We provide evidence that out of 18 NFPA tumors tested, 12 expressed HMGA2, but,
different from prolactinomas, only in two cases the upregulation of the gene could be associated with
amplification and/or rearrangement of the HMGA2 locus. Increased dosage of chromosome 12 was
found in the expressing and non-expressing NFPAs, confirming that this sole event is insufficient to
drive up activation of the HMGA2 gene. A role for chromosome 12 polysomy to promote structural
instability of HMGA2 is confirmed, but the mechanism via trisomy is less prevalent in the frequently
diploid NFPAs than in the usually hyperdiploid prolactinomas. Micro-rearrangements of HMGA2
gene not detectable by FISH analysis and/or sequence alterations could contribute to upregulation
of HMGA2 gene in pituitary adenomas of the NFPA subtype. However, it cannot be excluded that
the HMGA2 overexpression may be due, in some NFPA patients, to the same, still mainly unknown,
mechanisms responsible for HMGA2 overexpression in malignant neoplasias
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
G. M. Pierantoni, P. Finelli, E. Valtorta, D. Giardino, O. Rodeschini, F. Esposito, M. Losa, A. Fusco, L. Larizza
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