INHERITED MITOCHONDRIAL DNA MUTATIONS IN CANCER

摘要

A method is provided for identifying a subject likely to have, or at risk of developing a disease condition correlated with increased reactive oxygen species (ROS), including cancer, by identifying in the subject a missense mutation in a nucleic acid of Complex III, IV and/or V of the OXPHOS system. This invention also provides a method of identifying a likelihood of having a heritable predisposition to cancer by detecting a homoplasmic missense mutation in non-tumor tissue of an OXPHOS system gene. This invention also provides a method for detecting likelihood of having cancer, predisposition to cancer, and likelihood of passing a predisposition to cancer to progeny involving identifying in non-tumor tissue of the subject a missense mutation in a complex III, IV and/or V gene of the mitochondrial OXPHOS system. The mutation may be a nuclear or mitochondrial mutation. The invention has been exemplified with respect to prostate cancer. When the mutation is homoplasmic in non-tumor tissue this is an indication it is an inherited and inheritable trait, and that the subject is likely to pass on the mutation to her progeny in the case of mutations in mitochondrial DNA or his or her progeny in the case of mutations in nuclear DNA. Both homoplasmic and heteroplasmic mutations in non-tumor tissue can indicate the presence of cancer.