Systems and methods for diagnosing a predisposition to develop colon cancer

摘要

Systems and methods for diagnosing or characterizing a predisposition to colon cancer are provided. Cell nuclei may be evaluated for the presence or quantity of gamma-H2AX foci. Nucleic acids may be evaluated for the presence, type, or quantity of genomic instability or surrogates of dsDNA breaks such as ataxia telangiectasia mutated (ATM), Rad3-related protein (ATR), and Tumor suppressor p53-binding protein 1 (53BP1) in gamma-H2AX foci. Nucleic acids comprising a germline nucleic acid sequence of the ERCC6, WRN, TERT, and FAAP100 genes may be sequenced or probed to determine if the nucleic acid sequence includes one or more alterations that cause genomic instability, dsDNA breaks, or gamma-H2AX foci or otherwise predispose a subject to develop colon cancer.

主权项

1. A system for diagnosing a predisposition to develop cancer, comprising
an immunoblotting support, an immunofluorescence support, an immunohistochemistry support, an ELISA support, or a flow cytometry support comprising peripheral blood lymphocytes obtained from a human subject and permeabilized, a detectably-labeled antibody that specifically binds to gamma-H2AX foci, and a detector capable of detecting the detectably-labeled antibody bound to gamma-H2AX foci in the lymphocytes and of quantifying the level of gamma-H2AX foci in the lymphocytes based on detection of the detectably-labeled antibody; a metaphase spread or a karyotype obtained from the lymphocytes, and a detector capable of detecting the absence or presence and type of genomic instability from the metaphase spread or karyotype; a computer comprising an input for entering the level of gamma-H2AX foci in the lymphocytes and the type of genomic instability in the lymphocytes, a data structure comprising reference values for a level of gamma-H2AX foci and a type of genomic instability that together indicate a predisposition to develop colon cancer, a processor operably connected to the data structure, wherein the processor is programmed to compare the level of gamma-H2AX foci and type of genomic instability detected in the lymphocytes with the reference values and generate a diagnosis of whether the subject has or does not have a predisposition to develop colon cancer based on the comparison of the level of gamma-H2AX foci in the lymphocytes and the type of genomic instability in the lymphocytes with the reference values, and an output for providing the diagnosis to a user.