Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5

Maxwell P. Lee, Cynthia Reeves, Anna Schmitt, Kui Su, Timothy D. Connors, Ren Ju Hu, Sheri Brandenburg, Michael J. Lee, Glenn Miller, Andrew P. Feinberg

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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, p57(KIP2) 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 Gin. 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.

Original languageEnglish (US)
Pages (from-to)4155-4159
Number of pages5
JournalCancer Research
Issue number18
StatePublished - Sep 15 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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