Tiling resolution array CGH and high density expression profiling of urothelial carcinomas delineate genomic amplicons and candidate target genes specific for advanced tumors.

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Gudjonsson Sigurdur) > Tiling resolution a...

Details
MARC

Heidenblad, MarkusLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine (author)

Tiling resolution array CGH and high density expression profiling of urothelial carcinomas delineate genomic amplicons and candidate target genes specific for advanced tumors.

Article/chapterEnglish2008

Publisher, publication year, extent ...

2008-01-31
Springer Science and Business Media LLC,2008
electronicrdacarrier

Numbers

LIBRIS-ID:oai:lup.lub.lu.se:7429c8e4-f3e3-4a15-b560-c9959c6ccf83
https://lup.lub.lu.se/record/1042385URI
https://doi.org/10.1186/1755-8794-1-3DOI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

ABSTRACT: BACKGROUND: Urothelial carcinoma (UC) is characterized by nonrandom chromosomal aberrations, varying from one or a few changes in early-stage and low-grade tumors, to highly rearranged karyotypes in muscle-invasive lesions. Recent array-CGH analyses have shed further light on the genomic changes underlying the neoplastic development of UC, and have facilitated the molecular delineation amplified and deleted regions to the level of specific candidate genes. In the present investigation we combine detailed genomic information with expression information to identify putative target genes for genomic amplifications. METHODS: We analyzed 38 urothelial carcinomas by whole-genome tiling resolution array-CGH and high density expression profiling to identify putative target genes in common genomic amplifications. When necessary expression profiling was complemented with Q-PCR of individual genes. RESULTS: Three genomic segments were frequently and exclusively amplified in high grade tumors; 1q23, 6p22 and 8q22, respectively. Detailed mapping of the 1q23 segment showed a heterogeneous amplification pattern and no obvious commonly amplified region. The 6p22 amplicon was defined by a 1.8 Mb core region present in all amplifications, flanked both distally and proximally by segments amplified to a lesser extent. By combining genomic profiles with expression profiles we could show that amplification of E2F3, CDKAL1, SOX4, and MBOAT1 as well as NUP153, AOF1, FAM8A1 and DEK in 6p22 was associated with increased gene expression. Amplification of the 8q22 segment was primarily associated with YWHAZ (14-3-3-zeta) and POLR2K over expression. The possible importance of the YWHA genes in the development of urothelial carcinomas was supported by another recurrent amplicon paralogous to 8q22, in 2p25, where increased copy numbers lead to enhanced expression of YWHAQ (14-3-3-theta). Homozygous deletions were identified at 10 different genomic locations, most frequently affecting CDKN2A/CDKN2B in 9p21 (32%). Notably, the latter occurred mutually exclusive with 6p22 amplifications. CONCLUSION: The presented data indicates 6p22 as a composite amplicon with more than one possible target gene. The data also suggests that amplification of 6p22 and homozygous deletions of 9p21 may have complementary roles. Furthermore, the analysis of paralogous regions that showed genomic amplification indicated altered expression of YWHA (14-3-3) genes as important events in the development of UC.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

Lindgren, DavidLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Clinical Genetics,Department of Laboratory Medicine(Swepub:lu)kgen-dli (author)
Jonson, TordLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-tjo (author)
Liedberg, FredrikLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Urologi,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Urology,Lund University Research Groups(Swepub:lu)urok-fli (author)
Veerla, SrinivasLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Clinical Genetics,Department of Laboratory Medicine(Swepub:lu)klin-sve (author)
Chebil, Gunilla (author)
Gudjonsson, SigurdurLund University,Lunds universitet,Urologi,Forskargrupper vid Lunds universitet,Urology,Lund University Research Groups(Swepub:lu)urok-sgu (author)
Borg, ÅkeLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)onk-abo (author)
Månsson, WikingLund University,Lunds universitet,Urologi,Forskargrupper vid Lunds universitet,Urology,Lund University Research Groups(Swepub:lu)uro-wma (author)
Höglund, MattiasLund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Division of Clinical Genetics,Department of Laboratory Medicine(Swepub:lu)kgen-mho (author)
Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin (creator_code:org_t)

Related titles

In:BMC Medical Genomics: Springer Science and Business Media LLC1:Jan 311755-8794

Internet link

Find in a library

BMC Medical Genomics (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Heidenblad, Mark ...; Lindgren, David; Jonson, Tord; Liedberg, Fredri ...; Veerla, Srinivas; Chebil, Gunilla; show more...; Gudjonsson, Sigu ...; Borg, Åke; Månsson, Wiking; Höglund, Mattias; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Articles in the publication: BMC Medical Geno ...

By the university: Lund University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se