This study will evaluate soluble (free) DNA qualitatively and quantitatively in blood from patients with carcinoma of the pancreas and lung, as well as in an experimental model system. Soluble DNA is commonly present in blood from healthy individuals. Multiple studies have indicated that soluble DNA levels are increased in many patients with variable forms of cancer. In this project it is proposed to evaluate soluble DNA from patients with adenocarcinoma of the pancreas and lung and from nude mice with experimental tumors. A series of validation studies as well as investigations in patients with known and suspected cancers are proposed. It is planned to evaluate the DNA specimens for the presence of mutated K-ras genes which are commonly associated with pancreatic and pulmonary adenocarcinoma. For this analysis allele specific oligonucleotide primers will be used for amplification of the mutated genes by the polymerase chain reaction. Quantitative evaluations will be made of mutated K-ras genes and total DNA in plasma from patients and from mice with adenocarcinoma at different stages of clinical progression. In our first small series we have demonstrated that one can detect mutated K-ras sequences in the plasma of patients with pancreatic cancer which contain the identical mutation as present in the patient's tumor. The proposed project is an extension of these investigations. It is anticipated that these studies will provide a new series of tumor markers which can be measured in peripheral blood from patients with cancer. These markers may be very sensitive and specific indicators of tumor status which could be anticipated to be useful for diagnosis, measuring extent of tumor and response to treatment and/or determining prognosis.
Giacona, M B; Ruben, G C; Iczkowski, K A et al. (1998) Cell-free DNA in human blood plasma: length measurements in patients with pancreatic cancer and healthy controls. Pancreas 17:89-97 |
Rhodes, C H; Honsinger, C; Porter, D M et al. (1997) Analysis of the allele-specific PCR method for the detection of neoplastic disease. Diagn Mol Pathol 6:49-57 |
Rhodes, C H; Glantz, M J; Glantz, L et al. (1996) A comparison of polymerase chain reaction examination of cerebrospinal fluid and conventional cytology in the diagnosis of lymphomatous meningitis. Cancer 77:543-8 |