Multigene analysis of tumor samples
Inventors
Otto, Geoffrey Alan • Nahas, Michelle • Lipson, Doron
Assignees
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Publication Number
US-11959141-B2
Publication Date
2024-04-16
Expiration Date
Abstract
Methods of evaluating or providing a clonal profile of a subject interval, e.g., a subgenomic interval, or an expressed subgenomic interval (or of a cell containing the same), in a subject, are disclosed.
Core Innovation
The invention provides a sequencing method for tumor samples that integrates analysis of both immune and malignant cell nucleic acids. A nucleic acid library is acquired from a subject having a solid tumor, where the library comprises DNA molecules from a malignant cell of the solid tumor and RNA molecules or cDNA molecules derived from RNA molecules from a tumor infiltrating lymphocyte within the solid tumor.
The method contacts the library with a bait set to generate a library catch comprising selected members. The bait set captures an expressed subgenomic interval from the tumor infiltrating lymphocyte and a subgenomic interval from the malignant cell, or portions thereof, and the expressed subgenomic interval is associated with somatic hypermutation or a V(D)J somatic rearrangement.
The malignant-cell subgenomic interval is targeted from a gene other than an immunoglobulin, a T-cell receptor, or a B-cell receptor. The bait set provides capture under solution hybridization or surface-based hybridization conditions, and both the expressed subgenomic interval and the subgenomic interval from the malignant cell are sequenced within the library catch.
Claims Coverage
The provided material includes one independent sequencing method claim with three inventive features. It covers constructing a tumor-derived mixed nucleic acid library, capturing both an expressed immune-associated subgenomic interval and a malignant-cell subgenomic interval using a partitioned bait set, and sequencing occurrences of both interval types within the same library catch.
Tumor-derived mixed nucleic acid library
Acquiring a nucleic acid library comprising a plurality of members, each member comprising a nucleic acid derived from a sample taken from a subject having a solid tumor, wherein the library comprises DNA molecules from a malignant cell of the solid tumor, and RNA molecules or cDNA molecules derived from RNA molecules from a tumor infiltrating lymphocyte from the solid tumor.
Partitioned bait set capturing expressed immune and malignant-cell intervals
Contacting the library with a bait set to provide a library catch comprising a plurality of selected members comprising an expressed subgenomic interval from the tumor infiltrating lymphocyte and a subgenomic interval from the malignant cell, or portions thereof, wherein the bait set comprises a first portion that hybridizes to selected members comprising the expressed subgenomic interval or a portion thereof and a second portion that hybridizes to selected members comprising the subgenomic interval from the malignant cell, and wherein the expressed subgenomic interval is associated with somatic hypermutation or a V(D)J somatic rearrangement and the subgenomic interval from the malignant cell is from a gene other than an immunoglobulin, a T-cell receptor, or a B-cell receptor.
Sequencing both interval types from the library catch
Sequencing one or more occurrences of both the expressed subgenomic interval and the subgenomic interval from the malignant cell within the library catch.
The claim coverage centers on tumor-derived immune and malignant nucleic acids, bait-based capture using immune-expressed and malignant-specific portions, and sequencing of both captured interval types within the same library catch.
Stated Advantages
Documented Applications
No documented applications found
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