APOBEC Mutational Signature and Tumor Mutational Burden as Predictors of Clinical Outcomes and Treatment Response in Patients With Advanced Urothelial Cancer Article Swipe
Divya Natesan
,
Li Zhang
,
Henry J. Martell
,
Tanya Jindal
,
Patrick Devine
,
Bradley A. Stohr
,
Carlos Espinosa-Mendez
,
James P. Grenert
,
Jessica Van Ziffle
,
Nancy M. Joseph
,
Sarah E. Umetsu
,
Courtney Onodera
,
Michelle L. Turski
,
Emily Chan
,
Arpita Desai
,
Rahul Aggarwal
,
Anthony Wong
,
Sima P. Porten
,
Jonathan Chou
,
Terence W. Friedlander
,
Lawrence Fong
,
Eric J. Small
,
E. Alejandro Sweet‐Cordero
,
Vadim S. Koshkin
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2022.816706
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fonc.2022.816706
Introduction Tumor mutational burden (TMB) and APOBEC mutational signatures are potential prognostic markers in patients with advanced urothelial carcinoma (aUC). Their utility in predicting outcomes to specific therapies in aUC warrants additional study. Methods We retrospectively reviewed consecutive UC cases assessed with UCSF500, an institutional assay that uses hybrid capture enrichment of target DNA to interrogate 479 common cancer genes. Hypermutated tumors (HM), defined as having TMB ≥10 mutations/Mb, were also assessed for APOBEC mutational signatures, while non-HM (NHM) tumors were not assessed due to low TMB. The logrank test was used to determine if there were differences in overall survival (OS) and progression-free survival (PFS) among patient groups of interest. Results Among 75 aUC patients who had UCSF500 testing, 46 patients were evaluable for TMB, of which 19 patients (41%) had HM tumors and the rest had NHM tumors (27 patients). An additional 29 patients had unknown TMB status. Among 19 HM patients, all 16 patients who were evaluable for analysis had APOBEC signatures. HM patients (N=19) were compared with NHM patients (N=27) and had improved OS from diagnosis (125.3 months vs 35.7 months, p=0.06) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.04). Patients with APOBEC (N=16) were compared with remaining 56 patients, comprised of 27 NHM patients and 29 patients with unknown TMB, showing APOBEC patients to have improved OS from diagnosis (125.3 months vs 44.5 months, p=0.05) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.05). Neither APOBEC nor HM status were associated with response to immunotherapy. Conclusions In a large, single-institution aUC cohort assessed with UCSF500, an institutional NGS panel, HM tumors were common and all such tumors that were evaluated for mutational signature analysis had APOBEC signatures. APOBEC signatures and high TMB were prognostic of improved OS from diagnosis and both analyses also predicted inferior outcomes with chemotherapy treatment.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fonc.2022.816706
- https://www.frontiersin.org/articles/10.3389/fonc.2022.816706/pdf
- OA Status
- gold
- Cited By
- 13
- References
- 28
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4220839377
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4220839377Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fonc.2022.816706Digital Object Identifier
- Title
-
APOBEC Mutational Signature and Tumor Mutational Burden as Predictors of Clinical Outcomes and Treatment Response in Patients With Advanced Urothelial CancerWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-03-07Full publication date if available
- Authors
-
Divya Natesan, Li Zhang, Henry J. Martell, Tanya Jindal, Patrick Devine, Bradley A. Stohr, Carlos Espinosa-Mendez, James P. Grenert, Jessica Van Ziffle, Nancy M. Joseph, Sarah E. Umetsu, Courtney Onodera, Michelle L. Turski, Emily Chan, Arpita Desai, Rahul Aggarwal, Anthony Wong, Sima P. Porten, Jonathan Chou, Terence W. Friedlander, Lawrence Fong, Eric J. Small, E. Alejandro Sweet‐Cordero, Vadim S. KoshkinList of authors in order
- Landing page
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https://doi.org/10.3389/fonc.2022.816706Publisher landing page
- PDF URL
-
https://www.frontiersin.org/articles/10.3389/fonc.2022.816706/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.frontiersin.org/articles/10.3389/fonc.2022.816706/pdfDirect OA link when available
- Concepts
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APOBEC, Medicine, Oncology, Internal medicine, Cancer, Chemotherapy, Cholesterol, Apolipoprotein BTop concepts (fields/topics) attached by OpenAlex
- Cited by
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13Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 3, 2023: 4, 2022: 3Per-year citation counts (last 5 years)
- References (count)
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28Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7599999904632568 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.91010237 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |