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(American Journal of Pathology. 2000;156:651-659.)
© 2000 American Society for Investigative Pathology

Regular Articles

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

Elisabeth Edström^*, Eija Mahlamäki, Brita Nord, Magnus Kjellman^*, Ritva Karhu, Anders Höög^§, Nikolai Goncharov^¶, Bin Tean Teh, Martin Bäckdahl^* and Catharina Larsson

From the Departments of Surgery,^*
Molecular Medicine,
and Clinical Pathology,^§
Karolinska Hospital, Stockholm, Sweden; the Laboratory for Cancer Genetics,
Institute of Medical Technology, University of Tampere, Tampere, Finland; and the Institute for Endocrinological Research,^¶
Russian Medical Academy, Moscow, Russia

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.

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