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A characteristic pattern of mutations that reveals what caused them: tobacco, UV, a broken repair gene.
A mutational signature is a characteristic pattern of mutations that reveals what caused them, whether tobacco, ultraviolet light or a broken repair gene. The COSMIC catalogue names them: SBS1 for ageing, SBS3 for HRD, SBS4 for tobacco, SBS7 for UV, SBS2 and SBS13 for APOBEC, and SBS6 and SBS15 for mismatch repair loss. Signature 3 identifies HRD beyond BRCA, and APOBEC signatures predict certain resistance mutations, which motivates ideas on APOBEC inhibitors during targeted therapy and on blocking error-prone repair. Signatures require Whole-exome & whole-genome sequencing, and the term links to the COSMIC collection, Gad Getz, the TCGA Pan-Cancer Atlas paper and the pathways on chromosomal instability and clonal evolution.
Showing the technology this term belongs to: Whole-exome & whole-genome sequencing.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
The exome-level TMB here (0.82 per megabase) is an order of magnitude below panel estimates, a warning against comparing TMB across assays; and the survival signal sits in the microenvironment, which is where immunotherapy biomarkers for this disease may have to be found.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
TMB-high is uncommon but not negligible in TNBC, rises at relapse, and the tumour-agnostic pembrolizumab indication makes it worth measuring on a metastatic biopsy.
It gives the sequencing report a prognostic reading that does not depend on a repeat biopsy: an EGFR-mutant cancer that also carries RB1 and TP53 alterations will stop responding sooner and should be watched for a change of histology.
The FUSCC cohort is the East Asian reference and the basis of the FUTURE subtype-guided umbrella trial; its LAR findings point to CDK4/6 and HER2-mutant strategies rather than PARP inhibitors for that subtype.
It sets the baseline the adenoma-carcinoma sequence starts from and warns against reading a driver mutation found in tissue, or in stool or blood, as evidence of cancer.
It is the best population-based estimate of how much TNBC is homologous recombination deficient, shows that most of it is not germline BRCA, and argues that whole-genome sequencing at diagnosis could stratify trials and pick out the low group that needs something other than DNA-damaging chemotherapy.
Shares Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes, A standard evolvability score for every tumour, Merkel cell polyomavirus (MCPyV) status, Mutation.
Shares HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures, Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study, Enabling characteristic: genome instability and mutation, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection.
Shares HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures, Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma, Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection.
Shares Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma, Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection, Whole genomes redefine the mutational landscape of pancreatic cancer.
Shares HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures, Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study, Enabling characteristic: genome instability and mutation, Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection.
Shares Integrative molecular characterisation of gallbladder cancer reveals micro-environment-associated subtypes, Prevalence and mutational determinants of high tumor mutation burden in breast cancer, Rizvi 2015: the mutational landscape determines who responds to PD-1 blockade in lung cancer, Gallbladder cancer.
Shares Turn off the error-prone repair that manufactures resistance mutations, Enabling characteristic: genome instability and mutation, Whole genomes redefine the mutational landscape of pancreatic cancer, Mutagenesis & mutational signatures.
Shares Hollstein 1991: p53 mutations in human cancers, Cancer genome landscapes: about 140 driver genes, and each tumour needs only a handful, Driver and passenger mutations: the refined somatic mutation theory, Somatic mutation theory of cancer.