MDM2-Containing Double Minute Chromosomes And Methods Therefore
AssigneeFive3 Genomics, LLC
InventorsJohn Zachary Sanborn, Charles Joseph Vaske, Stephen Charles Benz
Life of this patent
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Abstract
Contemplated systems and methods allow for computational genomic analysis using paired-end sequence analysis and split read refinement to thereby identify high-confidence breakpoints associated with high copy numbers and orientation of rearrangements, which is then the basis for full reconstruction of double minutes (DM). In especially preferred aspects, the DM will also include an oncogene or tumor suppressor gene, and/or may be found in blood or blood derived fluids.
Claims24
A method of analyzing genomic data, comprising:
- determining a relative copy number between a tumor genomic sequence and a matched normal genomic sequence;
- identifying putative breakpoints in the tumor genomic sequence and the matched normal genomic sequence;
- refining the putative breakpoints to identify a breakpoint location and an orientation of the tumor genomic sequence;
- using a read support threshold to confirm the breakpoint as a significant breakpoint;
- using the relative copy number, the significant breakpoint, and the orientation to determine a genomic arrangement having a circular solution.
A method of analyzing genomic data, comprising:
- associating a copy number of a tumor genomic sequence with a breakpoint in the tumor genomic sequence upon reaching a read support threshold for the breakpoint;
- determining orientation of the tumor genomic sequence;
- and
- determining genomic arrangement using the copy number, position of the breakpoint, and orientation of the tumor genomic sequence.
A method of analyzing genomic data of a solid tumor, comprising:
- obtaining from a patient a biological fluid and isolating at least a portion of a tumor genome from the biological fluid;
- and
- determining if a region surrounding an oncogene exhibit a clustered pattern of breakpoints indicative of an amplified double minute.
A method of de-novo diagnosing a neoplastic disease, comprising:
- obtaining a biological sample from a patient and isolating a nucleic acid from the sample;
- analyzing the nucleic acid for a copy number of a genomic sample and a breakpoint in the genomic sample;
- associating the copy number of the genomic sequence with the breakpoint in the genomic sequence upon reaching a read support threshold for the breakpoint;
- determining orientation of the genomic sequence;
- and
- determining genomic arrangement using the copy number, position of the breakpoint, and the orientation of the genomic sequence;
- and
- using the genomic arrangement to determine likelihood for the neoplastic disease.
Dependencies are inferred from the claim text.