Comparative Genomic Hybridization Reveals Frequent Losses of Chromosomes 1p and 3q in Pheochromocytomas and Abdominal Paragangliomas, Suggesting a Common Genetic Etiology

Abstract

Pheochromocytomas and abdominal paragangliomas are rare, catecholamine-producing tumors that arise from the chromaffin cells derived from the neural crest. We used comparative genomic hybridization (CGH) to screen for copy number changes in 23 pheochromocytomas and 11 abdominal paragangliomas. The pattern of copy number changes was similar between pheochromocytomas and paragangliomas, with the most consistent finding being loss of 1cen-p31, which was detected in 28/34 tumors (82%). Losses were also found on 3q22-25 (41%), 11p (26%), 3p13-14 (24%), 4q (21%), 2q (15%), and 11q22-23 (15%), and gains were detected on 19p (26%), 19q (24%), 17q24-qter (21%), 11cen-q13 (15%), and 16p (15%). Losses of 1p and 3q were detected in the majority of tumors, whereas gains of 19p and q, 17q, and 16p were seen only in tumors with six or more CGH alterations. This progression of genetic events did not correspond with the conversion to a malignant phenotype. CGH alterations involving chromosome 11 were more frequent in the malignant tumors, compared with the benign tumors (9/12 versus 3/16). In summary, we propose that pheochromocytomas and abdominal paragangliomas, which share many clinical features, also have a common genetic origin and that the loss of 1cen-p31 represents an early and important event in tumor development.

CGH and CD 44/MIB-1 immunohistochemistry are helpful to distinguish metastasized from nonmetastasized sporadic pheochromocytomas

“…The suppressor gene p73 on 1p 36 32 which in neuroblastomas is clearly associated with a poor prognosis 27 seems to be of lesser importance in PCC. 2 In this study, gains on 12q (6/0) and 20q (7/2) and losses of 9p (4/0) were found in 10-22% of all cases with a statistical predominance in metastasized tumors. However, these results are not strong enough to support a definite correlation and need to be confirmed by further investigations.…”

“…[2][3][4] In those studies, the number of malignant adrenal PCC investigated was low (four, respectively, 10 sporadic malignant adrenal PCC) and the PASS scale had not yet been introduced.…”

Multiple locations on chromosome 3 are the targets of specific deletions in uveal melanoma

“…A region of common deletion on chromosome 3 has been described in uveal melanomas at 3q24-26, 19 a site that is infrequently affected in most tumours but is deleted in osteosarcomas, paragangliomas, and pheochromocytomas. [26][27][28] An additional tumour with a deletion involving 3q25.1-ter has also been reported in a single case of uveal melanoma, consistent with this region harbouring a TSG. 25 Here we report the screening of 52 cases of uveal melanoma for partial deletions of chromosome 3, the findings of which confirm previously reported commonly deleted regions at 3p25 and 3p11-14.…”

MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas

“…The gain of 16p region in malignant pheochromocytomas has been previously described. 36 As the histological analysis of pheochromocytomas for the establishment of malignancy and for the prediction of tumor recurrence is unreliable, miR-1225-3p might be of clinical importance for selecting patients with potentially recurring pheochromocytomas. Patients harboring tumors overexpressing miR-1225-3p should be regularly screened.…”