Document Detail


Landscape of somatic allelic imbalances and copy number alterations in human lung carcinoma.
MedLine Citation:
PMID:  23023297     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Lung cancer is the worldwide leading cause of death from cancer and has been shown to be a heterogeneous disease at the genomic level. To delineate the genomic landscape of copy number alterations, amplifications, loss-of-heterozygosity, tumor ploidy and copy-neutral allelic imbalance in lung cancer, microarray-based genomic profiles from 2141 tumors and cell lines including adenocarcinomas (AC, n=1206), squamous cell carcinomas (SqCC, n=467), large cell carcinomas (LCC, n=37) and small cell lung carcinomas (SCLC, n=88) were assembled from different repositories. Copy number alteration differences between lung cancer histologies were confirmed in 285 unrelated tumors analyzed by BAC aCGH. Tumor ploidy patterns were validated by DNA flow cytometry analysis of 129 unrelated cases. 89 recurrent copy number alterations (55 gains, 34 losses) were identified harboring genes with gene expression putatively driven by gene dosage through integration with gene expression data for 496 cases. 13 and 26 of identified regions discriminated AC/SqCC and AC/SqCC/SCLC, respectively, while 48 regions harbored recurrent (n>15) high-level amplifications comprising established and putative oncogenes, differing in frequency and co-amplification patterns between histologies. Lung cancer histologies displayed differences in patterns/frequency of copy number alterations, genomic architecture, loss-of-heterozygosity, copy-neutral allelic imbalance, and tumor ploidy, with AC generally displaying less copy number alterations and allelic imbalance. Moreover, a strong association was demonstrated between different types of copy number alterations and allelic imbalances with tumor aneuploidy. In summary, these analyses provide a comprehensive overview of the landscape of genomic alterations in lung cancer, highlighting differences but also similarities between subgroups of the disease. © 2012 Wiley-Liss, Inc.
Authors:
Johan Staaf; Sofi Isaksson; Anna Karlsson; Mats Jönsson; Leif Johansson; Per Jönsson; Johan Botling; Patrick Micke; Bo Baldetorp; Maria Planck
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 UICC.
Affiliation:
Department of Oncology, Clinical Sciences, Lund University and Skåne University Hospital, Barngatan 2B, SE 22185 Lund, Sweden; CREATE Health Strategic Center for Translational Cancer Research, Lund University, BMC C13, SE 22184, Lund, Sweden.
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