DETECTION OF EXTRACELLULAR TUMOR-ASSOCIATED NUCLEIC ACID IN BLOOD PLASMA OR SERUM USING NUCLEIC ACID AMPLIFICATION ASSAYS

摘要

This invention relates to detection of specific extracellular nucleic acid inplasma or serum fractions of human or animal bloodassociated with neoplastic or proliferative disease. Specifically, theinvention relates to detection of nucleic acid derived from mutantoncogenes or other tumor-associated DNA, and to those methods of detecting andmonitoring extracellular mutant oncogenes or tumor--associatedDNA found in the plasma or serum fraction of blood by using rapid DNAextraction followed by nucleic acid amplification withor without enrichment for mutant DNA. In particular, the invention relates tothe detection, identification, or monitoring of the existence,progression or clinical status of benign, premalignant, or malignant neoplasmsin humans or other animals that contain a mutation that isassociated with the neoplasm through detection of the mutated nucleic acid ofthe neoplasm in plasma or serum fractions. The inventionpermits the detection of extracellular, tumor-associated nucleic acid in theserum or plasma of humans or other animals recognized ashaving a neoplastic or proliferative disease or in individuals without anyprior history or diagnosis of neoplastic or proliferative disease.The invention provides the ability to detect extracellular nucleic acidderived from genetic sequences known to be associated with neoplasia,such as oncogenes, as well as genetic sequences previously unrecognized asbeing associated with neoplastic or proliferative disease. Theinvention thereby provides methods for early identification of colorectal,pancreatic, lung, breast, bladder, ovarian, lymphoma and all othermalignancies carrying tumor-related mutations of DNA and methods formonitoring cancer and other neoplastic disorders in humans andother animals.