Tag: Mutation Signature

HRD Signatures

[PMID: 29262283] [New England Journal of Medicine]

Signatures of DNA-Repair Deficiencies in Breast Cancer

Mini review of HRDetect and Paz’s paper.


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”


[PMID:28288110] [Nature Methods]

HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures

“Recently, somatic substitution, insertion/deletion and rearrangement patterns, or ‘mutational signatures’, were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples.”