Genetic Alterations in Human Lung Cancer

---

1. Genetic model of lung cancer progression

To understand the molecular processes and pathways of, and contributing factors to, lung cancer progression, genetic alterations in various stages of lung cancer cells have been studied, since these alterations can be regarded as molecular footprints representing the individual processes of multistage lung carcinogenesis. A genetic model of lung cancer was constructed based on the results of our analyses of molecular footprints of lung cancer cells.




2. Genetic model of lung adenocarcinoma development

Adenocarcinoma (ADC) is the most common histological subtype of lung cancer. By analyzing genetic alterations in small-sized lung ADCs of < 2 cm at their maximum diameter, a model for the development and progression of early-staged lung ADC was constructed based on the results in our laboratory.



3. Whole genome scanning of tumor suppressor genes

To identify novel tumor suppressor genes involved in human lung carcinogenesis, a whole genome scanning for chromosomal homozygous deletion has been undertaken in our laboratory. We identified a homozygous deletion on chromosome 22q12.1 in a small cell lung carcinoma cell line and isolated a novel myosin family gene, MYO18B, from this region. This gene was inactivated in approximately 50% of lung cancer by deletion, mutation, and methylation. Restoration of MYO18B expression in lung cancer cell lines suppressed anchorage-independent growth, therefore, MYO18B is considered to act as a lung tumor suppressor gene. We also recently identified the PTPRD gene encoding a receptor-type protein tyrosine phosphatase as a candidate for tumor suppressor gene from a homozygous deletion cluster region at chromosome 9p23.