title: Recurrent genomic alterations in benign and malignant pheochromocytomas and paragangliomas revealed by whole-genome array comparative genomic hybridization analysis.
abstract: Pheochromocytomas and abdominal paragangliomas are adrenal and extra-adrenal catecholamine-producing tumours. They arise due to heritable cancer syndromes, or more frequently occur sporadically due to an unknown genetic cause. The majority of cases are benign, but malignant tumours are observed. Previous comparative genomic hybridization (CGH) and loss of heterozygosity studies have shown frequent deletions of chromosome arms 1p, 3q and 22q in pheochromocytomas. We applied high-resolution whole-genome array CGH on 53 benign and malignant pheochromocytomas and paragangliomas to narrow down candidate regions as well as to identify chromosomal alterations more specific to malignant tumours. Minimal overlapping regions (MORs) were identified on 16 chromosomes, with the most frequent MORs of deletion (> or = 32%) occurring on chromosome arms 1p, 3q, 11p/q, 17p and 22q, while the chromosome arms 1q, 7p, 12q and 19p harboured the most common MORs of gain (> or = 14%). The most frequent MORs (61-75%) in the pheochromocytomas were identified at 1p, and the four regions of common losses encompassed 1p36, 1p32-31, 1p22-21 and 1p13. Tumours that did not show 1p loss generally demonstrated aberrations on chromosome 11. Gain of chromosomal material was significantly more frequent among the malignant cases. Moreover, gain at 19q, trisomy 12 and loss at 11q were positively associated with malignant pheochromocytomas, while 1q gain was commonly observed in the malignant paragangliomas. Our study revealed novel and narrow recurrent chromosomal regions of loss and gain at several autosomes, a prerequisite for identifying candidate tumour suppressor genes and oncogenes involved in the development of adrenal and extra-adrenal catecholamine-producing tumours.
authors.affiliation: Department of Surgical Sciences, Uppsala University Hospital Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden. johanna.sandgren@surgsci.uu.se
authors.forename: Johanna
authors.initials: J
authors.lastname: Sandgren
authors.forename: Teresita
authors.initials: T
authors.lastname: Diaz de Ståhl
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.forename: Uwe
authors.initials: U
authors.lastname: Menzel
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Piotrowski
authors.forename: Helena
authors.initials: H
authors.lastname: Nord
authors.forename: Martin
authors.initials: M
authors.lastname: Bäckdahl
authors.forename: Nimrod B
authors.initials: NB
authors.lastname: Kiss
authors.forename: Michael
authors.initials: M
authors.lastname: Brauckhoff
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Ola
authors.initials: O
authors.lastname: Hessman
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Göran
authors.initials: G
authors.lastname: Akerström
authors.forename: Carl
authors.initials: C
authors.lastname: Bruder
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
authors.forename: Gunnar
authors.initials: G
authors.lastname: Westin
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D055028:Comparative Genomic Hybridization; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction