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The transcriptional map of the common eliminated region 1 (C3CER1) in 3p21.3
Hajnalka Kiss1, Ying Yang, Csaba Kiss
1Microbiology and Tumor Biology Center (MTC), Karolinska Institutet, S-17177, Stockholm, Sweden. Hajnalka.Kiss@mtc.ki.se
Abstract:
Occurrence of chromosome 3p deletions in a large number of human tumours suggests the existence of uncharted tumour suppressor gene(s). We previously applied a functional assay, named the Elimination test (Et), for the identification of regions containing tumour growth antagonising genes. This resulted in the definition of chromosome 3 common eliminated region 1 (C3CER1) on 3p21.3, which is regularly eliminated from SCID-derived tumours. Systematic genomic sequencing of 11 PAC clones, combined with comparisons of genomic sequence against EST databases and PCR-based cloning of cDNA sequences allowed us to assemble a comprehensive transcriptional map of 1.4 Mb that includes 19 active genes and three processed pseudogenes. We report four novel genes: FYVE and coiled-coil domain containing 1 (FYCO1), transmembrane protein 7 (TMEM7), leucine-rich repeat-containing 2 (LRRC2) and leucine zipper protein 3 (LUZP3). A striking feature of C3CER1 is a presence of a cluster of eight chemokine receptor genes. Based on a new analysis of the microcell hybrid-derived panel of SCID tumours we also redefined the centromeric border of the C3CER1. It is now located within LRRC2 gene, which is a relative of RSP-1 (Ras Suppressor Protein 1). The detailed knowledge of gene content in C3CER1 is a prerequisite for functional analysis of these genes and understanding of their possible role in tumorigenesis.
Insights
Chromosome 3p deletions in tumors suggest unknown tumor suppressor genes. Researchers mapped chromosome 3 common eliminated region 1 (C3CER1), identifying four new genes and a cluster of chemokine receptors.
Area of Science:
- Genetics
- Cancer Biology
- Genomics
Background:
- Chromosome 3p deletions are frequent in human tumors, indicating the presence of unidentified tumor suppressor genes.
- The Elimination test (Et) previously identified chromosome 3 common eliminated region 1 (C3CER1) on 3p21.3 as a critical region in SCID-derived tumors.
Purpose of the Study:
- To create a comprehensive transcriptional map of the C3CER1 region.
- To identify novel genes within C3CER1 and refine its genomic boundaries.
- To investigate the role of genes in C3CER1 in tumorigenesis.
Main Methods:
- Systematic genomic sequencing of 11 PAC clones.
- Comparison of genomic sequences with EST databases.
- PCR-based cloning of cDNA sequences.
- Analysis of microcell hybrid-derived SCID tumors.
Main Results:
- A 1.4 Mb transcriptional map of C3CER1 was assembled, containing 19 active genes and three pseudogenes.
- Four novel genes were identified: FYCO1, TMEM7, LRRC2, and LUZP3.
- A cluster of eight chemokine receptor genes was found within C3CER1.
- The centromeric border of C3CER1 was redefined to be within the LRRC2 gene.
Conclusions:
- The detailed gene content of C3CER1 provides a foundation for functional studies.
- Understanding the genes in C3CER1 is crucial for elucidating their role in tumor suppression.
- This research contributes to the identification of novel cancer-related genes on chromosome 3p.
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