Tag: Mutation Signature

Mutation Signature and Replication Timing

[PMID: 30201020] [Genome Biology]

Mutational signature distribution varies with DNA replication timing and strand asymmetry

“we use somatic mutation signatures—each representing a mutagenic process—derived from 3056 patients spanning 19 cancer types to quantify the strand asymmetry of mutational signatures around replication origins and between early and late replicating regions… We observe that most of the detected mutational signatures are significantly correlated with the timing or direction of DNA replication. “


HRD Predicts BRCA1/2

[PMID: 29246904] [Clinical Cancer Research]

Homologous Recombination Deficiency and Platinum-Based Therapy Outcomes in Advanced Breast Cancer

WGS on 93 T/N (100x/60x) in advanced breast cancer. They called the mutation signatures and looked into how HRD predicts BRCA1/2 status and outcomes of platinum-based chemo. Basically they used HRDetect to generate a score (aggregated metric) to represent six HRD signatures for correlation tests. They also examined how signatures differ across PAM50 subtypes.

Hypermutation in Cancer

[PMID: 29056344] [Cell]

Comprehensive Analysis of Hypermutation in Human Cancer

“an extensive assessment of mutation burden through sequencing analysis of >81,000 tumors from pediatric and adult patients” “Mutation burden analysis reveals new drivers of hypermutation in POLE and POLD1.” “Replication repair deficiency was a major contributing factor. ” “Unbiased clustering, based on mutational context, revealed clinically relevant subgroups regardless of the tumors’ tissue of origin, highlighting similarities in evolutionary dynamics leading to hypermutation.” “The order of mutational signatures identified previous treatment and germline replication repair deficiency”