Abstract: The disclosure features in some aspects methods for identifying subjects with constitutional mismatch repair deficiency (CMMRD), a mismatch repair deficiency (MMD) cancer, a polymerase proofreading deficiency (PPD) cancer, and/or a MMD&PPD cancer. The disclosure also features in some aspects methods for predicting response of a subject to immunotherapy.

Abstract: There is provided a method of profiling a tumour, the method comprising determining a relative proportion for each of 96 mutation types, wherein the 96 mutation types are defined as the six possible sequence changes C>A, C>G, C>T, T>A, T>C, or T>G in the context of each of four possible nucleotides (A, C, G, or T) at the position immediately 5? to the mutation and each of four possible nucleotides at the position immediately 3? to the mutation; assigning the tumour, using the determined relative proportion for each of the 96 mutation types, to at least one of eight clusters defined herein; and determining at least one tumour characteristic based on the assignment to a cluster.

Abstract: There is provided a method of profiling a tumour, the method comprising determining a relative proportion for each of 96 mutation types, wherein the 96 mutation types are defined as the six possible sequence changes C>A, C>G, C>T, T>A, T>C, or T>G in the context of each of four possible nucleotides (A, C, G, or T) at the position immediately 5? to the mutation and each of four possible nucleotides at the position immediately 3? to the mutation; assigning the tumour, using the determined relative proportion for each of the 96 mutation types, to at least one of eight clusters defined herein; and determining at least one tumour characteristic based on the assignment to a cluster.

Abstract: A method of diagnosing cancer in a mammal is provided. The method includes the steps of determining in a nucleic acid-containing sample from the mammal the degree of DNA methylation of a target region within the hTERT promoter from the nucleotide at about position ?157 to the nucleotide at about position ?580, or a corresponding target region in a TERT promoter in a mammal other than a human, to yield a sample methylation signature, determining the baseline degree of DNA methylation of the target region in a control sample to yield a control methylation signature, comparing the sample methylation signature to the control methylation signature and rendering a diagnosis of cancer when there is at least 1.5 times more methylation in the sample methylation signature as compared to the control methylation signature. Methods of determining tumour grade and progression, predicting survival and determining whether or not a mammal is a candidate for telomerase-targeted or demethylation therapy are also provided.

Abstract: A method of diagnosing cancer in a mammal is provided. The method includes the steps of determining in a nucleic acid-containing sample from the mammal the degree of DNA methylation of a target region within the hTERT promoter from the nucleotide at about position ?157 to the nucleotide at about position ?580, or a corresponding target region in a TERT promoter in a mammal other than a human, to yield a sample methylation signature, determining the baseline degree of DNA methylation of the target region in a control sample to yield a control methylation signature, comparing the sample methylation signature to the control methylation signature and rendering a diagnosis of cancer when there is at least 1.5 times more methylation in the sample methylation signature as compared to the control methylation signature. Methods of determining tumour grade and progression, predicting survival and determining whether or not a mammal is a candidate for telomerase-targeted or demethylation therapy are also provided.

Abstract: A method of diagnosing cancer in a mammal is provided. The method includes the steps of determining in a nucleic acid-containing sample from the mammal the degree of DNA methylation of a target region within the hTERT promoter from the nucleotide at about position ?157 to the nucleotide at about position ?580, or a corresponding target region in a TERT promoter in a mammal other than a human, to yield a sample methylation signature, determining the baseline degree of DNA methylation of the target region in a control sample to yield a control methylation signature, comparing the sample methylation signature to the control methylation signature and rendering a diagnosis of cancer when there is at least 1.5 times more methylation in the sample methylation signature as compared to the control methylation signature. Methods of determining tumor grade and progression, predicting survival and determining whether or not a mammal is a candidate for telomerase-targeted or demethylation therapy are also provided.

Abstract: A method of diagnosing cancer in a mammal is provided. The method includes the steps of determining in a nucleic acid-containing sample from the mammal the degree of DNA methylation of a target region within the hTERT promoter from the nucleotide at about position ?157 to the nucleotide at about position ?580, or a corresponding target region in a TERT promoter in a mammal other than a human, to yield a sample methylation signature, determining the baseline degree of DNA methylation of the target region in a control sample to yield a control methylation signature, comparing the sample methylation signature to the control methylation signature and rendering a diagnosis of cancer when there is at least 1.5 times more methylation in the sample methylation signature as compared to the control methylation signature. Methods of determining tumour grade and progression, predicting survival and determining whether or not a mammal is a candidate for telomerase-targeted or demethylation therapy are also provided.