^
BIOMARKER:

APOBEC mutagenesis

1m
Journal • Checkpoint inhibition • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • CD8 (cluster of differentiation 8)
|
TP53 mutation • TMB-H • APOBEC mutagenesis
|
Tecentriq (atezolizumab)
2ms
"We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2- disease that associate with poor overall survival (p = 0.0092), and multiple PIK3CA mutations in HR + disease that associate with short progression free survival on fulvestrant (p = 0.0036)...In ER-positive breast cancer subclonal mutations were enriched in an APOBEC mutational signature, with second hit PIK3CA mutations acquired subclonally and at sites characteristic of APOBEC mutagenesis. This study utilises circulating tumour DNA analysis in a large clinical trial to demonstrate the subclonal diversification of pre-treated advanced breast cancer, identifying distinct mutational processes in advanced ER-positive breast cancer, and novel therapeutic opportunities."
Journal • Circulating tumor DNA
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
HER-2 positive • ER positive • PIK3CA mutation • HER-2 negative • ER mutation • APOBEC mutagenesis
|
Guardant360® CDx
|
fulvestrant
3ms
The results of this investigation suggest that the clinical behavior of a tumor, in particular response to neoadjuvant chemotherapy and DFS of therapy-resistant tumors, could be predicted by the composition of mutational signatures as an indicator of the individual genomic history of a tumor. After additional validations, mutational signatures might be used to identify tumors with an increased response rate to neoadjuvant chemotherapy and to define therapy-resistant subgroups for future therapeutic interventions.
Clinical • Journal
|
HRD (Homologous Recombination Deficiency)
|
HR positive • HRD • APOBEC mutagenesis
3ms
Based on genomic alterations, potential therapeutic targets were identified in 111/116 mUC patients, of which FGFR3 alterations (18%) and fusions (6%), and CDKN2A (44%), ERBB2 (20%), and TSC1 (14%) alterations were most common. By integrating the genomic and transcriptomic data, we propose potential novel therapeutic options per transcriptomic subtype, like addition of a TGF-β inhibitor to immune checkpoint inhibition for the stroma-rich and basal/squamous subtypes that showed the highest TGF-β pathway activity.Using WGS and RNAseq analyses, we provide a comprehensive overview of the molecular landscape of mUC that may serve as a reference for more subgroup-oriented and patient-specific research on the etiology of mUC and future drug development.
Tumor Mutational Burden • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • TSC1 (TSC complex subunit 1) • TGFB1 (Transforming Growth Factor Beta 1)
|
TP53 mutation • FGFR3 fusion • APOBEC mutagenesis
3ms
To model APOBEC mutagenesis in lung cancer, we have developed a novel lung cancer mouse model, by crossing the ROSA26LSL-APOBEC3B (A3B) mouse model with several different EGFR mutant mouse models. Using these models, we find that APOBEC3B expression is selected for post-TKI and contributes to resistance to TKI therapy.
Tumor Mutational Burden
|
EGFR (Epidermal growth factor receptor) • TMB (Tumor Mutational Burden)
|
EGFR mutation • APOBEC mutagenesis
3ms
Paired host and viral analyses revealed APOBEC-enriched somatic samples (higher APOBEC mutational burden, A3A expression, and A3A-associated RNA editing) also have higher viral APOBEC mutation rates, strongly supporting a direct link between APOBEC mutations in host and viral genomes. APOBEC-enriched samples also had higher IFN-γ scores, suggesting immune upregulation, possibly in response to viral infection.Using paired sequencing of somatic exomes, transcriptomes, and viral genomes of HPV+ HNSCC samples, here, we demonstrate concordance between tumor and viral APOBEC mutagenesis in HPV+ HNSCC, supporting existing hypotheses regarding the role of APOBEC in viral restriction and resultant off-target host-genome mutagenesis.
Tumor Mutational Burden
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • IFNG (Interferon, gamma) • APOB (Apolipoprotein B)
|
PIK3CA mutation • APOBEC mutagenesis
5ms
Taken together, our results suggest that the germline A3B deletion polymorphism, via the A3A-B hybrid isoform, contributes to APOBEC-mutagenesis in a significant proportion of Asian breast cancers. In addition, APOBEC somatic hypermutation, regardless of A3B background, may be an important clinical biomarker for Asian breast cancers.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
PIK3CA mutation • APOBEC mutagenesis
8ms
We demonstrate that APOBEC leads to alterations in genes known to be able to act as a driver in early and mBC and further facilitates endocrine resistance in mBC. Our results underscore the importance of APOBEC mutagenesis in the genomic evolution of BC.
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • APOB (Apolipoprotein B)
|
TP53 mutation • PIK3CA mutation • NF1 mutation • ARID1A mutation • KMT2C mutation • APOBEC mutagenesis
|
MSK-IMPACT
8ms
We demonstrate that APOBEC leads to alterations in genes known to be able to act as a driver in early and mBC and further facilitates endocrine resistance in mBC. Our results underscore the importance of APOBEC mutagenesis in the genomic evolution of BC.
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ARID1A (AT-rich interaction domain 1A) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • APOB (Apolipoprotein B)
|
TP53 mutation • PIK3CA mutation • NF1 mutation • ARID1A mutation • KMT2C mutation • APOBEC mutagenesis
|
MSK-IMPACT
9ms
Our study identified novel potential drivers within APOBEC-associated hotspot mutations in BCa reinforcing the importance of APOBEC mutagenesis in BCa. It could allow a better understanding of BCa biology and aetiology and have clinical implications such as AhR as a potential therapeutic target. Our results also challenge the dogma that all hotspot mutations are drivers and mostly gain-of-function mutations affecting oncogenes.
Journal
|
FGFR3 (Fibroblast growth factor receptor 3) • AHR (Aryl hydrocarbon receptor)
|
FGFR3 mutation • FGFR3 S249C • APOBEC mutagenesis
11ms
We identify eight processes, including a mutational signature caused by exposure to melphalan...We define four main patterns of activation-induced deaminase (AID) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutagenesis over time, including a subset of patients with evidence of prolonged AID activity during the pre-malignant phase, indicating antigen-responsiveness and germinal center reentry. Our findings provide a framework to study the etiology of multiple myeloma and explore strategies for prevention and early detection.
Journal
|
APOB (Apolipoprotein B)
|
APOBEC mutagenesis
|
melphalan
12ms
Multiple mechanisms may exist within HNSCC leading to APOBEC mutations including immune upregulation in response to neoantigens and viral infection, via induction of IFNy. These mechanisms may be additive and not mutually exclusive, which could explain higher levels of APOBEC mutations in HPV mediated HNSCC.
Journal • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden)
|
APOBEC mutagenesis
1year
CNAs occurring late in tumor evolution correlated with downstream transcriptomic and proteomic heterogeneity, although global proteomic heterogeneity was significantly greater than transcriptomic and CNA heterogeneity. These results illustrate key mechanisms underlying multi-dimensional heterogeneity in metastatic thoracic tumors.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • APOBEC mutagenesis
1year
This suggests that despite infection by a single oncogenic virus, HPVmOPSCCs may develop via multiple, disparate pathways. Of particular interest is the tumor pairs' clear discordance in APOBEC mutational burden, which challenges existing hypotheses on the role of APOBEC mutagenesis in this disease.
Clinical • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden)
|
APOBEC mutagenesis
VERI is free for non-commercial use, no login needed.
Content on this site is for research purposes only and is not intended  to be a substitute for medical advice.
For commercial access, including additional premium features, please contact us.
By using VERI, you are agreeing to our