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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
Author(s) -
Groet Jürgen,
Ives Jane H.,
Jones Tania A.,
Danton Malcolm,
Flomen Rachel H.,
Sheer Denise,
Hrašćan Reno,
Pavelić Krešimir,
Nižetić Dean
Publication year - 2000
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(200002)27:2<153::aid-gcc6>3.0.co;2-a
Subject(s) - biology , loss of heterozygosity , exon , gene , genetics , locus (genetics) , allele , microbiology and biotechnology
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. © 2000 Wiley‐Liss, Inc.