Document Detail


Total HLA class I loss in a sarcomatoid renal carcinoma cell line caused by the coexistence of distinct mutations in the two encoding beta2-microglobulin genes.
MedLine Citation:
PMID:  18704411     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In renal cell carcinoma (RCC), HLA class I downregulation has been found in about 40% of the lesions examined. Since only scanty information is available about the molecular basis of these defects, we have investigated the mechanism(s) underlying HLA class I antigen downregulation or loss in six RCC cell lines. Five of them express HLA class I antigens although at various levels; on the other hand, HLA class I antigens are not detectable on the remaining cell line, the RCC52 cell line, belonging to a sarcomatoid subtype, even following incubation with IFN-gamma. beta(2)-microglobulin (beta(2) m) was not detected in RCC52 cells. Surprisingly, RCC52 cells harbor two mutations in the beta ( 2 ) m genes in exon 1: a single G deletion (delG) in codon 6, which introduces a premature stop at codon 7, and a CT dinucleotide deletion (delCT), which leads to a premature stop at codon 55. Analysis of eight clonal sublines isolated from the RCC52 cell line showed that the two beta ( 2 ) m gene mutations are carried separately by RCC52 cell subpopulations. The delG/delCT double mutations were detected in two sublines with a fibroblast-like morphology, while the delCT mutation was detected in the remaining six sublines with an epithelial cell morphology. Furthermore, loss of heterozygosity (LOH) of the beta ( 2 ) m gene at STR D15S-209 was found only in the epithelioid subpopulation, indicating loss of one copy of chromosome 15. Immunostaining results of the tumor lesion from which the cell line RCC52 was originated were consistent with the phenotyping/molecular findings of the cultured cells. This is the first example of the coexistence of distinct beta ( 2 ) m defects in two different tumor subpopulations of a RCC, where loss of one copy of chromosome 15 occurs in one of the subpopulations with total HLA class I antigen loss.
Authors:
Chin-Hsuan Hsieh; Ya-Jan Hsu; Chien-Chung Chang; Hsin-Chun Liu; Kun-Lung Chuang; Cheng-Keng Chuang; See-Tong Pang; Kenichiro Hasumi; Soldano Ferrone; Shuen-Kuei Liao
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-15
Journal Detail:
Title:  Cancer immunology, immunotherapy : CII     Volume:  58     ISSN:  1432-0851     ISO Abbreviation:  Cancer Immunol. Immunother.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-01-07     Completed Date:  2009-01-28     Revised Date:  2014-07-29    
Medline Journal Info:
Nlm Unique ID:  8605732     Medline TA:  Cancer Immunol Immunother     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  395-408     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma / metabolism*
Cell Line, Tumor
Epithelial Cells / metabolism
Gene Expression Regulation, Neoplastic*
Genes, MHC Class I*
HLA Antigens / metabolism*
Humans
Interferon-gamma / metabolism
Kidney Neoplasms / metabolism*
Loss of Heterozygosity
Mice
Mutation*
Sarcoma / metabolism*
beta 2-Microglobulin / genetics*,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 CA110249/CA/NCI NIH HHS; R01 CA110249-03/CA/NCI NIH HHS; R01CA110249/CA/NCI NIH HHS; R01CA67108/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/HLA Antigens; 0/beta 2-Microglobulin; 82115-62-6/Interferon-gamma
Comments/Corrections

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