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1. Supplementary Figure legends from Low-Coverage Exome Sequencing Screen in Formalin-Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid

Author

Jiri Zavadil, Bojan Jelaković, Arthur P. Grollman, Magali Olivier, Kathleen G. Dickman, Adriana Heguy, Andrea Fernandes, Viktoria S. Sidorenko, Shahrokh F. Shariat, James McKay, Igor Dolgalev, Damir Dittrich, Maja Mišić, Krešimir Karlović, Catherine Voegele, Florence Le Calvez-Kelm, Nathalie Forey, Stephanie Villar, Geoffroy Durand, Evanguelos Xylinas, Karla Tomić, Maude Ardin, Sandra Karanović, and Xavier Castells

Abstract

Supplementary Figure legends

Published
2023
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2. Supplementary Figure S1 from Low-Coverage Exome Sequencing Screen in Formalin-Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid

Author

Jiri Zavadil, Bojan Jelaković, Arthur P. Grollman, Magali Olivier, Kathleen G. Dickman, Adriana Heguy, Andrea Fernandes, Viktoria S. Sidorenko, Shahrokh F. Shariat, James McKay, Igor Dolgalev, Damir Dittrich, Maja Mišić, Krešimir Karlović, Catherine Voegele, Florence Le Calvez-Kelm, Nathalie Forey, Stephanie Villar, Geoffroy Durand, Evanguelos Xylinas, Karla Tomić, Maude Ardin, Sandra Karanović, and Xavier Castells

Abstract

Supplementary Figure S1. Identification of AA signature by ultra-low coverage sequencing reads.

Published
2023
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3. Supplementary Figure S3 from Low-Coverage Exome Sequencing Screen in Formalin-Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid

Author

Jiri Zavadil, Bojan Jelaković, Arthur P. Grollman, Magali Olivier, Kathleen G. Dickman, Adriana Heguy, Andrea Fernandes, Viktoria S. Sidorenko, Shahrokh F. Shariat, James McKay, Igor Dolgalev, Damir Dittrich, Maja Mišić, Krešimir Karlović, Catherine Voegele, Florence Le Calvez-Kelm, Nathalie Forey, Stephanie Villar, Geoffroy Durand, Evanguelos Xylinas, Karla Tomić, Maude Ardin, Sandra Karanović, and Xavier Castells

Abstract

Supplementary Figure S3. LC-WES analysis of patients with multiple tumors.

Published
2023
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4. Supplementary Figure S2 from Low-Coverage Exome Sequencing Screen in Formalin-Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid

Author

Jiri Zavadil, Bojan Jelaković, Arthur P. Grollman, Magali Olivier, Kathleen G. Dickman, Adriana Heguy, Andrea Fernandes, Viktoria S. Sidorenko, Shahrokh F. Shariat, James McKay, Igor Dolgalev, Damir Dittrich, Maja Mišić, Krešimir Karlović, Catherine Voegele, Florence Le Calvez-Kelm, Nathalie Forey, Stephanie Villar, Geoffroy Durand, Evanguelos Xylinas, Karla Tomić, Maude Ardin, Sandra Karanović, and Xavier Castells

Abstract

Supplementary Figure S2. Mutation profiles obtained from LC-WES using SOLiD 5500xl sequencer.

Published
2023
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5. Supplemental Material (for review only) File - Supplementary Tables 1-5. from Low-Coverage Exome Sequencing Screen in Formalin-Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid

Author

Jiri Zavadil, Bojan Jelaković, Arthur P. Grollman, Magali Olivier, Kathleen G. Dickman, Adriana Heguy, Andrea Fernandes, Viktoria S. Sidorenko, Shahrokh F. Shariat, James McKay, Igor Dolgalev, Damir Dittrich, Maja Mišić, Krešimir Karlović, Catherine Voegele, Florence Le Calvez-Kelm, Nathalie Forey, Stephanie Villar, Geoffroy Durand, Evanguelos Xylinas, Karla Tomić, Maude Ardin, Sandra Karanović, and Xavier Castells

Abstract

Supplementary Table S1: Clinicopathological and epidemiological patient data and urothelial tumor sample description. Supplementary Table S2: Complete list of annotated SBS identified in all LC-WES analyzed urothelial tumors (HiSeq2500 data only). Supplementary Table S3: GO and KEGG Classification of genes mutated by non-synonymous A:T>T:A mutations. Supplementary Table S4: List of cancer driver genes found recurrently mutated in the EN and Taiwan UTUC sample sets. Supplementary Table S5: GO and KEGG classification of the recurrently mutated cancer driver genes (see Figure 3B).

Published
2023
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6. Supplementary Methods from Low-Coverage Exome Sequencing Screen in Formalin-Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid

Author

Jiri Zavadil, Bojan Jelaković, Arthur P. Grollman, Magali Olivier, Kathleen G. Dickman, Adriana Heguy, Andrea Fernandes, Viktoria S. Sidorenko, Shahrokh F. Shariat, James McKay, Igor Dolgalev, Damir Dittrich, Maja Mišić, Krešimir Karlović, Catherine Voegele, Florence Le Calvez-Kelm, Nathalie Forey, Stephanie Villar, Geoffroy Durand, Evanguelos Xylinas, Karla Tomić, Maude Ardin, Sandra Karanović, and Xavier Castells

Abstract

Supplementary Methods

Published
2023
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7. Low-coverage exome sequencing screen in formalin- Fixed Paraffin-Embedded Tumors Reveals Evidence of Exposure to Carcinogenic Aristolochic Acid

Author

Viktoria S. Sidorenko, Adriana Heguy, James McKay, Geoffroy Durand, Catherine Voegele, Kathleen G. Dickman, Evanguelos Xylinas, Andrea Fernandes, Karla Tomić, Magali Olivier, Krešimir Karlović, Arthur P. Grollman, Sandra Karanović, Florence Le Calvez-Kelm, Jiri Zavadil, Maude Ardin, Stephanie Villar, Nathalie Forey, Shahrokh F. Shariat, Damir Dittrich, Igor Dolgalev, Xavier Castells, Maja Mišić, and Bojan Jelaković

Subjects
Nonsynonymous substitution, Pathology, medicine.medical_specialty, Tissue Fixation, Epidemiology, aristolochic acid, urothelial carcinoma, formalin-fixed paraffin-embedded tumors, whole-exome sequencing, mutational signature, Aristolochic acid, Biology, Article, Nephropathy, chemistry.chemical_compound, Formaldehyde, Neoplasms, medicine, Humans, Exome, Transversion, Exome sequencing, Paraffin Embedding, Bladder cancer, Cancer, Sequence Analysis, DNA, medicine.disease, Oncology, chemistry, Carcinogens, Cancer research, Aristolochic Acids
Abstract

Background: Dietary exposure to cytotoxic and carcinogenic aristolochic acid (AA) causes severe nephropathy typically associated with urologic cancers. Monitoring of AA exposure uses biomarkers such as aristolactam-DNA adducts, detected by mass spectrometry in the kidney cortex, or the somatic A>T transversion pattern characteristic of exposure to AA, as revealed by previous DNA-sequencing studies using fresh-frozen tumors. Methods: Here, we report a low-coverage whole-exome sequencing method (LC-WES) optimized for multisample detection of the AA mutational signature, and demonstrate its utility in 17 formalin-fixed paraffin-embedded urothelial tumors obtained from 15 patients with endemic nephropathy, an environmental form of AA nephropathy. Results: LC-WES identified the AA signature, alongside signatures of age and APOBEC enzyme activity, in 15 samples sequenced at the average per-base coverage of approximately 10×. Analysis at 3 to 9× coverage revealed the signature in 91% of the positive samples. The exome-wide distribution of the predominant A>T transversions exhibited a stochastic pattern, whereas 83 cancer driver genes were enriched for recurrent nonsynonymous A>T mutations. In two patients, pairs of tumors from different parts of the urinary tract, including the bladder, harbored overlapping mutation patterns, suggesting tumor dissemination via cell seeding. Conclusions: LC-WES analysis of archived tumor tissues is a reliable method applicable to investigations of both the exposure to AA and its biologic effects in human carcinomas. Impact: By detecting cancers associated with AA exposure in high-risk populations, LC-WES can support future molecular epidemiology studies and provide evidence-base for relevant preventive measures. Cancer Epidemiol Biomarkers Prev; 24(12); 1873–81. ©2015 AACR.

Published
2015

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