Early lung cancer detection by DNA methylation phenotyping of sputum-derived cells
AssigneesCedars-Sinai Medical Center, The Regents of the University of California, US Govt Department of Veterans Affairs
InventorsJian Tajbakhsh, Fariborz Mortazavi
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Abstract
In certain embodiments, this application discloses methods for detecting lung cancer. The method includes characterization of cells extracted from human sputum, which is a valuable tissue surrogate and source of upper respiratory cells that become cancerous early in the process of lung cancer development. The method includes the staining of extracted cells with fluorescent reporters that produce a specific pattern in the nuclei of labeled cells, which can be made visible by light microscopy. The pattern is relevant to a type of epigenetic coding of DNA known as DNA methylation, which changes in specific cells of the lung during cancer development, in comparison to normal respiratory cells.
Claims18
A method, comprising:
- obtaining a biological sample from a subject, the biological sample including a plurality of cells;
- determining a 5-methylcytosine (5mC) content and a global DNA (gDNA) content in a nucleus of each of the plurality of cells;
- generating and displaying a scatter plotting of the 5mC content and gDNA-content for the nucleus;
- determining a spatial nuclear co-distribution of the 5mC content and gDNA content in the nucleus of each of the plurality of cells;
- determining that a cell of the plurality of cells is hypomethylated if:
- the 5mC content in the nucleus of the cell is lower than a 5mC content from one or more non-cancerous or non-precancerous reference cells by 25% or more;
- and/or
- a regression-line angle of the scatter plotting is smaller than a regression-line angle of a scatter plotting in the one or more non-cancerous or non-precancerous reference cells, when the gDNA content defines x-axis, the 5mC content defines y-axis, and the regression-line angle is with the x-axis of the scatter plotting;
- based at least in part on a percentage of determined hypomethylated cells in the plurality of cells exceeding a threshold, determining that the subject has a high risk of developing clinically verifiable cancer;
- and
- treating the subject for cancer by (i) administering chemotherapy, (ii) administering radiation therapy, (iii) performing surgery, or (iv) any combination thereof.
Dependencies are inferred from the claim text.