Multigene analysis of tumor samples

A sequencing method comprising:

• (a) acquiring a nucleic acid library comprising a plurality of members, each member of the plurality 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;
• (b) 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;
• and
• (c) sequencing one or more occurrences of both the expressed subgenomic interval and the subgenomic interval from the malignant cell within the library catch.