18 research outputs found
Losses of chromosomes 1p and 3q are early genetic events in the development of sporadic pheochromocytomas
Despite several loss of heterozygosity studies, a comprehensive genomic
survey of pheochromocytomas is still lacking. To identify DNA copy number
changes which might be important in tumor development and progression and
which may have diagnostic utility, we evaluated genetic aberrations in 29
sporadic adrenal and extra-adrenal pheochromocytomas (19 clinically benign
tumors and 10 malignant lesions). Comparative genomic hybridization was
performed using directly fluorochrome-conjugated DNA extracted from frozen
(16) and paraffin-embedded (13) tumor tissues. The most frequently
observed changes were losses of chromosomes 1p11-p32 (86%), 3q (52%), 6q
(34%), 3p, 17p (31% each), 11q (28%), and gains of chromosomes 9q (38%)
and 17q (31%). No amplification was identified and no difference between
adrenal and extra-adrenal tumors was detected. Progression to malignant
tumors was strongly associated with deletions of chromosome 6q (60% versus
21% in clinically benign lesions, P = 0.0368) and 17p (50% versus 21%).
Fluorescence in situ hybridization confirmed the comparative genomic
hybridization data of chromosomes 1p, 3q, and 6q, and revealed aneuploidy
in some tumors. Our results suggest that the development of
pheochromocytomas is associated with specific genomic aberrations, such as
losses of 1p, 3q, and 6q and gains of 9q and 17q. In particular, tumor
suppressor genes on chromosomes 1p and 3q may be involved in early
tumorigenesis, and deletions of chromosomes 6q and 17p in progression to
malignancy