SAN FRANCISCO—In a study from Johns Hopkins University Medical School, one third of sporadic lung adenocarcinomas were found to have the inactivated LKB1/STK11 gene. A germ-line mutation in this gene has been shown to result in Peutz-Jegher’s syndrome. Patients with this autosomally dominant disease have an increased risk of developing malignancies. Montserrat Sanchez-Cespedes, PhD, now a senior scientist at the Spanish National Cancer Center, Madrid, presented the study at the 93rd Annual Meeting of the American Association for Cancer Research (abstract 720).
The Johns Hopkins researchers had previously determined that there were high rates of deletions on the short arm of chromosome 19 in lung adenocarcinoma samples. Dr. Sanchez-Cespedes and her colleagues then used 18 highly polymorphic microsatellite markers to identify the alteration as occurring in the 5-Mb interval between the telomeric end and microsatellite marker D19S216, which contains the LKB1/STK11 gene.
Analysis of 41 lung tumors selected for loss of heterozygosity at chromosome 19p revealed somatic mutations in 8 tumors, all predicting a truncated LKB1/STK11 protein. All of the 8 mutations were found in the 24 lung adenocarcinoma specimens.
"We hope that these findings will help in the future in the diagnosis of this tumor . . . and can be used as a target for the development of new therapies," Dr. Sanchez-Cespedes said. The researchers are studying more tumor specimens to increase the statistical weight of the initial findings and plan to compare tumor samples with clinical data to determine if the LKB1/STK11 mutation is related to survival or response to therapy.
