Naslov
Narrowing of the Region of Allelic Loss in 21q11-21 in Aquamous Non-Small Cell Lung Carcinoma and Cloning of a Novel Ubiquitin-Specific protease Gene From the Deleted Segment
(Narrowing of the region of allelic loss in 21q11-21 in aquamous non-small cell lung carcinoma and cloning of a novel ubiquitin-specific protease gene from the deleted segment)

Autori
Groet, Jurgen ; Ives, Jane H. ; Jones, Tania A. ; Danton, Malcolm ; Flomen, Rachel H. ; Sheer, Denise ; Hrašćan, Reno ; Pavelić, Krešimir ; Nižetić, Dean

Izvornik
Genes chromosomes cancer 27 (2000); 153-161

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
novel gene; USP21; squamous non-small carcinoma

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA