Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5.
Cancer Res
; 58(18): 4155-9, 1998 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-9751628
ABSTRACT
We previously reported the isolation of a 2.5 Mb tumor-suppressing subchromosomal transferable fragment (STF) from 11p15.5 and the identification of nine known genes and four novel genes within this STF. We now report the isolation of a fifth novel cDNA, tumor-suppressing STF cDNA 5, designated TSSC5, located within the STF. TSSC5 encodes a predicted protein of 424 amino acids. Sequence analysis suggests that TSSC5 is a membrane protein with 10 transmembrane segments, and it is located between two imprinted genes, p57KIP2 and TSSC3. Northern blot hybridization revealed a 1.6-kb transcript in multiple adult tissues and in fetal liver and kidney, consistent with a potential role in embryonal tumors. We also found that TSSC5 is imprinted with preferential expression from the maternal chromosome. Reverse transcription-PCR analysis of TSSC5 revealed frequent occurrence of aberrant RNA splicing, which deleted exons 4, 5, and 6 in Wilms' tumors. Mutational analysis of TSSC5 by direct DNA sequencing of exons revealed a base substitution of G1120A in a Wilms' tumor, matched normal kidney, and the patient's mother, changed Arg at codon 309 to Gln. The G1120A substitution thus represents either a rare polymorphism or a tumor-predisposing mutation, because the mutant allele was of maternal origin and preferentially expressed in the patient's tissue. A second base substitution, C892T, was found in a lung cancer, changing Ser at codon 233 to Phe. This substitution was absent from the matched normal tissue and thus represented a somatic mutation. We also found loss of heterozygosity in the lung cancer, suggesting that TSSC5 may be a conventional tumor suppressor gene in the adult human lung and an imprinted tumor suppressor gene in the fetal kidney.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 11
/
Genes Supressores de Tumor
/
Mutação
/
Proteínas de Neoplasias
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos