PMID- 10612803 OWN - NLM STAT- MEDLINE DCOM- 20000210 LR - 20220129 IS - 1045-2257 (Print) IS - 1045-2257 (Linking) VI - 27 IP - 2 DP - 2000 Feb TI - Narrowing of the region of allelic loss in 21q11-21 in squamous non-small cell lung carcinoma and cloning of a novel ubiquitin-specific protease gene from the deleted segment. PG - 153-61 AB - We examined 42 fresh non-small cell lung carcinomas for allelic loss using 4 microsatellite markers located in a 4.5 Mb region in 21q11-21, a gene-poor interval recently found by others to be homozygously deleted and exhibiting frequent allelic loss in lung cancer. We found allelic loss across the entire segment in 13/34 informative squamous carcinomas, with 2 cases showing loss in only part of the region. Analysis by fluorescence in situ hybridization of P1-derived artificial chromosomes from the region directly on paraffin sections of the tumor is in concordance with the loss of heterozygosity (LOH) results, and tentatively excludes a 2 Mb segment bearing 2 of the only 3 known genes in the area. Exon trapping in the remaining segment of loss led to identification and cloning of a novel gene spanning 150 kb within the deletion. The full-length gene encodes a protein of 1,055 amino acids with homology to ubiquitin-specific proteases across the eukaryotic evolutionary spectrum. The expressed protein acts as a de-ubiquitinating enzyme as proved by the ability to cleave ubiquitin from a model fusion protein. We found no mutations in the sequence of the functional domains of this gene in any of the LOH-exhibiting tumor DNA samples. It is, however, interesting that genes of the same superfamily have been reported on 3p21, a locus showing the most frequent allelic instability and deletions in lung cancer. Genes Chromosomes Cancer 27:153-161, 2000. CI - Copyright 2000 Wiley-Liss, Inc. FAU - Groet, J AU - Groet J AD - Centre for Applied Molecular Biology, School of Pharmacy, University of London, London, United Kingdom. FAU - Ives, J H AU - Ives JH FAU - Jones, T A AU - Jones TA FAU - Danton, M AU - Danton M FAU - Flomen, R H AU - Flomen RH FAU - Sheer, D AU - Sheer D FAU - Hrascan, R AU - Hrascan R FAU - Pavelic, K AU - Pavelic K FAU - Nizetic, D AU - Nizetic D LA - eng SI - GENBANK/AF134213 GR - A3585/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 RN - 0 (Recombinant Fusion Proteins) RN - 0 (Ubiquitins) RN - 9007-49-2 (DNA) RN - EC 3.4.- (Endopeptidases) RN - EC 3.4.19.12 (Ubiquitin-Specific Proteases) SB - IM MH - Amino Acid Sequence MH - Carcinoma, Non-Small-Cell Lung/*genetics MH - Carcinoma, Squamous Cell/*genetics MH - Chromosomes, Human, Pair 21/*genetics MH - Cloning, Molecular MH - DNA/chemistry/genetics MH - Endopeptidases/*genetics/metabolism MH - Exons MH - Genetic Vectors MH - Humans MH - In Situ Hybridization, Fluorescence MH - Loss of Heterozygosity MH - Lung Neoplasms/*genetics MH - Microsatellite Repeats MH - Molecular Sequence Data MH - Recombinant Fusion Proteins/genetics/metabolism MH - Sequence Analysis, DNA MH - Sequence Deletion MH - Sequence Homology, Amino Acid MH - Ubiquitin-Specific Proteases MH - Ubiquitins/genetics/metabolism EDAT- 1999/12/29 00:00 MHDA- 1999/12/29 00:01 CRDT- 1999/12/29 00:00 PHST- 1999/12/29 00:00 [pubmed] PHST- 1999/12/29 00:01 [medline] PHST- 1999/12/29 00:00 [entrez] AID - 10.1002/(SICI)1098-2264(200002)27:2<153::AID-GCC6>3.0.CO;2-A [pii] PST - ppublish SO - Genes Chromosomes Cancer. 2000 Feb;27(2):153-61.