title: Loss of a small region around the PTEN locus is a major chromosome 10 alteration in prostate cancer xenografts and cell lines.
abstract: We examined 11 prostate cancer xenografts and 4 cell lines for chromosome 10 alterations. Conventional comparative genomic hybridization (CGH) and array-based CGH revealed a pattern of loss of distal 10p, gain of proximal 10p and 10q, and loss of distal 10q. In addition, array CGH identified 2 high-level amplifications in the cell line PC3, homozygous deletions of PTEN in PC3 and in the xenografts PCEW, PC133, and PC324, and small single- or double-copy deletions around PTEN in PCEW, PC82, PC324, PC346, and LNCaP. Allelotype analysis confirmed all 10p losses, 5 of 6 large 10q losses, the homozygous deletions, and the small regions of one copy loss. MXI1, DMBT1, and KLF6 were excluded as important tumor-suppressor genes. The sizes of homozygous deletions around PTEN ranged from 1.2 Mbp (PC133) to <30 kbp (PTEN exon 5 in PC295). The regions of small single- or double-copy loss around PTEN were all less than 4.5 Mbp. The loss of 1 or 2 copies of PTEN was always accompanied by loss of the distal flanking gene FLJ11218 and, in most cases, by loss of the proximal flanking genes MINPP1, PAPSS2, and FLJ14600. Furthermore, differential expression was detected for FLJ11218 and PAPSS2. Complete deletion or inactivating mutation of PAPSS2 was found in at least 3 samples. In addition to 4 homozygous deletions, 1 missense mutation was detected in FLJ11218. In conclusion, our data provide evidence that loss of a small region around PTEN is the major chromosome 10 alteration in prostate cancer xenografts and cell lines. In some of the samples, PTEN inactivation was accompanied by loss of 1 MINPP1 allele, loss of 1 copy, mutation, or low expression of PAPSS2, and most frequently by loss of 1 or 2 copies or low expression of FLJ11218.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Karin G
authors.initials: KG
authors.lastname: Hermans
authors.forename: Dirk C
authors.initials: DC
authors.lastname: van Alewijk
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
authors.forename: Wytske
authors.initials: W
authors.lastname: van Weerden
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: Jan
authors.initials: J
authors.lastname: Trapman
mesh_terms: D024509:3' Flanking Region / Q000235:genetics; D024506:5' Flanking Region / Q000235:genetics; D000483:Alleles; D000818:Animals; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D005819:Genetic Markers