title: Novel tumor suppressor loci on 6q22-23 in primary central nervous system lymphomas.
abstract: Deletions on the long arm of chromosome 6 (6q) are one of the most common chromosomal alterations in systemic high-grade non-Hodgkin's lymphomas. However, the locations of allelic deletions and their roles have not yet been reported in primary central nervous system lymphomas (PCNSLs), most of which are classed as non-Hodgkin's lymphoma. We thus performed fine loss of heterozygosity (LOH) mapping of 6q in 29 samples of surgically resected PCNSLs using 39 microsatellite markers to identify commonly deleted regions. LOH was found at 1 or more loci at 6q22-23 in 19 samples (66%); furthermore, 18 of these samples shared a deletion in the same small ( approximately 140 kb) region flanked by D6S1030 and D6S1690, a region in which the human R-PTP-kappa gene (PTPRK) is reported to be located. Reverse transcription-PCR analysis of the mRNA from 4 cases with 6q deletions confirmed loss of this gene, and loss of PTPRK expression was observed in 76% (22 of 29) of tumors with immunohistochemistry. In addition, LOH on 6q22-q23 significantly correlated to shorter patient survival (12.8 +/- 4.3 versus 23.4 +/- 3.5 months; P < 0.0001). Our results suggest that a 140-kb deletion located at 6q22-23 may contain the putative tumor suppressor, PTPRK, that appears to be relevant to the pathogenesis and prognosis of PCNSLs.
authors.affiliation: Department of Pathology, Nara Medical University, 634-8521 Nara, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Munehiro
authors.initials: M
authors.lastname: Kishi
authors.forename: Toshisuke
authors.initials: T
authors.lastname: Sakaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
authors.forename: Keiji
authors.initials: K
authors.lastname: Shimada
authors.forename: Eiwa
authors.initials: E
authors.lastname: Ishida
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism; D002872:Chromosome Deletion; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D017027:Protein Tyrosine Phosphatases