title: Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH.
abstract: Pheochromocytoma is a predominantly sporadic neuroendocrine tumor derived from the adrenal medulla. Previous low resolution LOH and metaphase-CGH studies reported the loss of chromosomes 1p, 3q, 17p and 22q at various frequencies. However, the molecular mechanism(s) behind development of sporadic pheochromocytoma remains largely unknown. We have applied high-resolution tiling-path microarray-CGH with the primary aim to characterize copy number imbalances affecting chromosome 22 in 66 sporadic pheochromocytomas. We detected copy number alterations on 22q at a frequency of 44%. The predominant finding was monosomy 22 (30%), followed by terminal deletions in 8 samples (12%) and a single interstitial deletion. We further applied a chromosome 1 tiling-path array in 7 tumors with terminal deletions of 22q and found deletions of 1p in all cases. Our overall results suggest that at least 2 distinct regions on both 22q and 1p are important in the tumorigenesis of sporadic pheochromocytoma. A large proportion of pheochromocytomas also displayed indications of cellular heterogeneity. Our study is to our knowledge the first array-CGH study of sporadic pheochromocytoma. Future analysis of this tumor type should preferably be performed in the context of the entire human genome using genome-wide array-CGH, which is a superior methodological approach. Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jarbo
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Buckley
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Piotrowski
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Mantripragada
authors.forename: Magdalena
authors.initials: M
authors.lastname: Benetkiewicz
authors.forename: Teresita
authors.initials: T
authors.lastname: Diaz de Ståhl
authors.forename: Cordelia F
authors.initials: CF
authors.lastname: Langford
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.forename: Martin
authors.initials: M
authors.lastname: Bäckdahl
authors.forename: Janos
authors.initials: J
authors.lastname: Geli
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Westin
authors.forename: Göran
authors.initials: G
authors.lastname: Akerström
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dumanski
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010673:Pheochromocytoma / Q000235:genetics*