Identification of a 428-kb homozygously deleted region disrupting the SEZ6L gene at 22q12.1 in a lung cancer cell line

Oncogene. 2000 Dec 14;19(54):6251-60. doi: 10.1038/sj.onc.1204031.


Frequent allelic losses on chromosome 22q in small cell lung carcinomas (SCLCs) and advanced non-small cell lung carcinomas indicate the presence of tumor suppressor gene(s) on this chromosome arm. We detected a homozygous deletion at 22q12.1 in a SCLC cell line, Lu24. Cloning of the breakpoints of the Lu24 deletion revealed that the deletion was interstitial and 428, 131 bp in size. The deleted region contained the SEZ6L (Seizure 6-like) gene, whose structure had been partially determined by the chromosome 22 sequencing project. We determined the full length cDNA sequence for the SEZ6L gene based on the genomic sequence for the SEZ6L locus using the GENSCAN program and the RT - PCR method. The deduced SEZ6L protein was a transmembrane protein of 1024 amino acids with multiple domains involved in protein - protein interaction and signal transduction. SEZ6L expression was detected in a variety of human tissues, including lung, while its expression was detected in 14 (30%) of 46 lung cancer cell lines examined. Missense mutations were detected in three (7%) of the 46 cell lines, and a 1 bp deletion in the polypyrimidine tract preceding exon 4 was detected in one (2%) of 46 primary lung cancers. Therefore, it is possible that genetic and/or epigenetic SEZ6L alterations are involved in the development and/or progression in a subset of lung cancer, although functional analysis of the SEZ6L gene as well as molecular analysis of other genes in the homozygously deleted region is necessary to understand the pathogenetic significance of 22q deletions in human lung carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Chromosome Deletion
  • Chromosomes, Human, Pair 22*
  • Cloning, Molecular
  • Gene Expression
  • Genes, Tumor Suppressor
  • Homozygote
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Point Mutation
  • Polymorphism, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured


  • Carrier Proteins
  • Membrane Proteins
  • SEZ6L protein, human

Associated data

  • GENBANK/AB041736