Monitoring health and disease status using clonotype profiles

摘要

There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, autoimmune disease and other conditions. Identified biomarkers can be used to determine and/or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. In particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.

主权项

1. A method of monitoring a lymphoid neoplasm in a patient by one or more patient-specific clonotypes correlated with the lymphoid neoplasm, the method comprising the steps of:
(a) obtaining a sample from the patient comprising T-cells and/or B-cells; (b) amplifying molecules of nucleic acid from the T-cells and/or B-cells of the sample, the molecules of nucleic acid comprising recombined DNA sequences from T-cell receptor genes or immunoglobulin genes; (c) sequencing the amplified molecules of nucleic acid to form a clonotype profile, wherein the sequencing comprises at least 10,000 reads per run; and (d) determining from the clonotype profile a presence, absence and/or level of the one or more patient-specific clonotypes correlated with the lymphoid neoplasm and phylogenic clonotypes thereof.