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Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer
1Department of Medicine III, Osaka University Medical School, Suita, Japan.
Abstract:
Previously, we have reported that the inactivation of putative tumor-suppressor gene(s) on chromosome 5q21-22 may play an important role in the progression of lung cancer. Here, we describe the establishment of a yeast artificial chromosome (YAC) contig that spans 8-10 Mb at the 5q21-22 region. Six cosmid contigs have also been established in this YAC contig. About 35 exon-like fragments have been detected by exon-amplification, direct screening, cross-species hybridization, and searches of a database. Thus far, 14 cDNAs have been isolated, and two of them coincide with known genes, viz., cysteine dioxygenase I and geranylgeranyltransferase I. The other 12 cDNAs are considered to be novel genes. Two of these novel cDNA show partial homology to known genes, viz., semaphorin CD100 and the 28S rRNA gene. In addition, four known genes, including APC (adenomatous polyposis coli), MCC (mutated in colorectal cancer), proto-oncogene tyrosine kinase FER, and genomic imprinted gene U2AF1-RS1, have also been mapped in this contig. This large contig and expression map should prove crucial in the identification of susceptibility gene(s) related to the progression of lung cancer.
Insights
Researchers mapped genes on chromosome 5q21-22, identifying novel genes and known cancer-related genes. This genetic map aids in finding lung cancer susceptibility genes.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Inactivation of tumor-suppressor genes on chromosome 5q21-22 is implicated in lung cancer progression.
- A detailed genetic map of this region is essential for identifying causative genes.
Purpose of the Study:
- To establish a comprehensive yeast artificial chromosome (YAC) contig spanning the 5q21-22 region.
- To identify and map genes within this critical chromosomal area relevant to lung cancer.
Main Methods:
- Construction of an 8-10 Mb YAC contig and six cosmid contigs.
- Detection of exon-like fragments using exon-amplification and cross-species hybridization.
- Isolation and characterization of complementary DNAs (cDNAs) and mapping of known genes.
Main Results:
- Established a large YAC contig and expression map of the 5q21-22 region.
- Identified 14 cDNAs, including 12 novel genes, two with partial homology to known genes.
- Mapped four known genes, including APC, MCC, FER, and U2AF1-RS1, within the contig.
Conclusions:
- The developed genetic map provides a crucial resource for lung cancer research.
- Facilitates the identification of novel susceptibility genes involved in lung cancer progression.