Novel tumor suppressor loci on 6q22-23 in primary central nervous system lymphomas.
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.
Nakamura
Mitsutoshi
M
Department of Pathology, Nara Medical University, 634-8521 Nara, Japan.
Kishi
Munehiro
M
Sakaki
Toshisuke
T
Hashimoto
Hiroyuki
H
Nakase
Hiroyuki
H
Shimada
Keiji
K
Ishida
Eiwa
E
Konishi
Noboru
N
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
D012333:RNA, Messenger; D017027:Protein Tyrosine Phosphatases