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Article

Rare Occurrence of Aristolochic Acid Mutational Signatures in Oro-Gastrointestinal Tract Cancers

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Cheng Kin Ku Herbal Biodiversity & Medicine Program, SingHealth Duke-NUS Institute of Biodiversity Medicine, Singapore 169610, Singapore
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Cancer Discovery Hub, National Cancer Centre Singapore, Singapore 169610, Singapore
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Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore 169610, Singapore
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Division of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore
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Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
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Department of Surgery, New Taipei Municipal Tucheng Hospital, New Taipei City 236, Taiwan
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College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
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Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore
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Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
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Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
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Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
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Authors to whom correspondence should be addressed.
Academic Editors: Sonika Patial and Sonja M. Kessler
Cancers 2022, 14(3), 576; https://doi.org/10.3390/cancers14030576
Received: 6 December 2021 / Revised: 3 January 2022 / Accepted: 6 January 2022 / Published: 24 January 2022
(This article belongs to the Special Issue Environmental Carcinogenesis)
Aristolochic acids (AAs) are a family of carcinogenic phytochemical compounds commonly found in plants of the Aristolochia and Asarum genera. Comprehensive genomic profiling of genitourinary and hepatobiliary cancers has highlighted the widespread prevalence of Aristolochic acid (AA) signatures in cancer patients across parts of Asia, particularly in Taiwan. The aim of our study was to determine in oro-gastrointestinal tract cancers (OGITCs), the prevalence, role and significance that AA plays as a driver of tumorigenesis as AA-containing products are commonly administered orally. This suggests a possible etiological relationship between OGITCs. However, in this study, the rarity of AA mutational signatures in OGITCs suggests that AA is unlikely to drive carcinogenesis in OGITCs through direct exposure. Our study is valuable because it shows that AA exposure is not an equal driver of tumorigenesis in different organs and represents an important piece of information in the field.
Background: Aristolochic acids (AAs) are potent mutagens commonly found in herbal plant-based remedies widely used throughout Asian countries. Patients and Methods: To understand whether AA is involved in the tumorigenesis of the oro-gastrointestinal tract, we used whole-exome sequencing to profile 54 cases of four distinct types of oro-gastrointestinal tract cancer (OGITC) from Taiwan. Results: A diverse landscape of mutational signatures including those from DNA mismatch repair and reactive oxygen species was observed. APOBEC mutational signatures were observed in 60% of oral squamous cell carcinomas. Only one sample harbored AA mutational signatures, contradictory to prior reports of cancers from Taiwan. The metabolism of AA in the liver and urinary tract, transient exposure time, and high cell turnover rates at OGITC sites may explain our findings. Conclusion: AA signatures in OGITCs are rare and unlikely to be a major contributing factor in oro-gastrointestinal tract tumorigenesis. View Full-Text
Keywords: carcinogens; mutagenesis; next generation sequencing; genomics; aristolochic acid carcinogens; mutagenesis; next generation sequencing; genomics; aristolochic acid
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MDPI and ACS Style

Lim, A.H.; Chan, J.Y.; Yu, M.-C.; Wu, T.-H.; Hong, J.H.; Ng, C.C.Y.; Low, Z.J.; Liu, W.; Vikneswari, R.; Sung, P.-C.; Fan, W.-L.; Teh, B.T.; Hsieh, S.-Y. Rare Occurrence of Aristolochic Acid Mutational Signatures in Oro-Gastrointestinal Tract Cancers. Cancers 2022, 14, 576. https://doi.org/10.3390/cancers14030576

AMA Style

Lim AH, Chan JY, Yu M-C, Wu T-H, Hong JH, Ng CCY, Low ZJ, Liu W, Vikneswari R, Sung P-C, Fan W-L, Teh BT, Hsieh S-Y. Rare Occurrence of Aristolochic Acid Mutational Signatures in Oro-Gastrointestinal Tract Cancers. Cancers. 2022; 14(3):576. https://doi.org/10.3390/cancers14030576

Chicago/Turabian Style

Lim, Abner H., Jason Y. Chan, Ming-Chin Yu, Tsung-Han Wu, Jing H. Hong, Cedric C.Y. Ng, Zhen J. Low, Wei Liu, Rajasegaran Vikneswari, Pin-Cheng Sung, Wen-Lang Fan, Bin T. Teh, and Sen-Yung Hsieh. 2022. "Rare Occurrence of Aristolochic Acid Mutational Signatures in Oro-Gastrointestinal Tract Cancers" Cancers 14, no. 3: 576. https://doi.org/10.3390/cancers14030576

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