Personalized tumor biomarkers

A method of identifying and using a tumor biomarker for a human patient, the method comprising:

• (a) preparing a mate-paired library of mate-paired nucleic acid fragments from a solid tumor sample obtained from a human patient wherein the mate-paired nucleic acid fragments comprise two genomic tags that are co-linear, non-contiguous in a segment and are separated by about 1.2 kb to about 1.7 kb in the solid tumor sample:
• (b) assaying the mate-paired library by next generation sequencing to determine sequences of the mate-paired nucleic acid fragments;
• (c) mapping the sequences for the mate-paired nucleic acid fragments to a reference to determine a tumor-specific, somatically acquired rearrangement in the solid tumor sample obtained from the human patient relative to the reference, wherein the reference is a normal human genome and wherein the sequences for the mate-paired nucleic acid fragments align perfectly and are uniquely localized in the reference;
• and
• (d) identifying a breakpoint associated with the tumor-specific, somatically acquired rearrangement, wherein the tumor-specific, somatically acquired rearrangement occurs between two genomic tags are (i) at different locations or in a different orientation within a chromosome or (ii) on different chromosomes in the solid tumor sample of the human patient than in the reference;
• (e) obtaining a plasma sample from the human patient after the tumor sample is obtained;
• (f) amplifying a DNA fragment from the plasma sample to create an amplified DNA fragment, wherein the DNA fragment is amplified using rearrangement-specific amplification primers that hybridize to priming sites on opposite sides of the breakpoint such that the amplified DNA fragment is of an expected size only when the DNA fragment comprises the breakpoint associated with the tumor-specific, somatically acquired rearrangement;
• and
• (g) determining an amount of the amplified DNA fragment comprising the breakpoint associated with the tumor-specific, somatically acquired rearrangement in the plasma sample.