Losses of chromosomes 1p and 3q are early genetic events in the development of sporadic pheochromocytomas

Citation
H. Dannenberg et al., Losses of chromosomes 1p and 3q are early genetic events in the development of sporadic pheochromocytomas, AM J PATH, 157(2), 2000, pp. 353-359
Citations number
45
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
00029440 → ACNP
Volume
157
Issue
2
Year of publication
2000
Pages
353 - 359
Database
ISI
SICI code
0002-9440(200008)157:2<353:LOC1A3>2.0.ZU;2-1
Abstract
Despite several loss of heterozygosity studies, a comprehensive genomic sur vey of pheochromocytomas is still lacking. To identify DNA copy number chan ges which might be Important in tumor development and progression and which may have diagnostic utility, we evaluated genetic aberrations in 29 sporad ic adrenal and extra-adrenal pheochromocytomas (19 clinically benign tumors and 10 malignant lesions). Com parative genomic hybridization was performe d 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 ampl ification was identified and no difference between adrenal and extra-adrena l tumors was detected. Progression to malignant tumors was strongly associa ted with deletions of chromosome 6q (60% versus 21% in clinically benign le sions, P = 0.0368) and 17p (50% versus 21%). Fluorescence in situ hybridiza tion confirmed the comparative genomic hybridization data of chromosomes 1p , 3q, and 6q, and revealed aneuploidy in some tumors. Our results suggest t hat the development of pheochromocytomas is associated with specific genomi c 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 involve d in early tumorigenesis, and deletions of chromosomes 6q and 17p in progre ssion to malignancy.