Methods of treating cancers having a biallelic loss of function or gene overexpression mutation

A method of identifying a cell from a subject as having a biallelic mutation in a target gene, the method comprising:

• from read counts for a plurality of consistently covered single nucleotide variants (SNVs) comprising homozygous and heterozygous consistently covered SNVs obtained from sequencing a sample comprising the cell and from reference read counts, determining an integer total copy number of a locus segment within a target gene region in the cell from the subject and/or two integer allele-specific copy numbers of the locus segment, the target gene region comprising the mutation, wherein the reference read counts are from a panel of normal samples,
• wherein the cell is identified as having a biallelic mutation for a target gene,
• if at least one of the integer total copy number and the integer allele-specific copy numbers is 0, provided that the remaining target gene allele, if present, comprises the mutation, or
• if none of the integer allele-specific copy numbers is 0 and target gene alleles are present, each of the target gene alleles independently having the mutation.

A method of identifying a cell from a subject as amplified for a target gene, the method comprising:

• from read counts for a plurality of consistently covered single nucleotide variants (SNVs) comprising homozygous and heterozygous consistently covered SNVs obtained from sequencing a sample comprising the cell and from reference read counts, determining a total copy number of a locus segment within a target gene region in the cell from the subject and a sample ploidy, the target gene region comprising the mutation, wherein the reference read counts are from a panel of normal samples,
• wherein the cell is identified as amplified for a target gene,
• if the total copy number is at least double the sample ploidy, or
• if the total copy number is greater than the sample ploidy by at least two.

A method of identifying a target mutation in a cell from a subject as being germline or somatic, the method comprising:

• from read counts for a plurality of consistently covered single nucleotide variants (SNVs) comprising homozygous and heterozygous consistently covered SNVs obtained from sequencing a sample comprising the cell and from reference read counts, determining an observed allele fraction of a locus segment within a target gene region in the cell from the subject, the target gene region comprising the target mutation;
• determining expected allele fractions for a germline target mutation and for a somatic target mutation;
• comparing the observed allele fraction to the expected allele fractions to identify the most probable of the germline and somatic mutations;
• and
• identifying the target mutation as germline or somatic as that which is the most probable for the germline and somatic mutations.