Frontiers in Oncology (Jun 2024)
Transcriptomic convergence despite genomic divergence drive field cancerization in synchronous squamous tumors
- Qiu Xuan Tan,
- Qiu Xuan Tan,
- Qiu Xuan Tan,
- Nicholas B. Shannon,
- Weng Khong Lim,
- Weng Khong Lim,
- Jing Xian Teo,
- Daniel R. Y. Yap,
- Sze Min Lek,
- Joey W. S. Tan,
- Joey W. S. Tan,
- Joey W. S. Tan,
- Shih Jia J. Tan,
- Josephine Hendrikson,
- Josephine Hendrikson,
- Josephine Hendrikson,
- Ying Liu,
- Ying Liu,
- Ying Liu,
- Gillian Ng,
- Gillian Ng,
- Gillian Ng,
- Clara Y. L. Chong,
- Clara Y. L. Chong,
- Clara Y. L. Chong,
- Wanyu Guo,
- Wanyu Guo,
- Wanyu Guo,
- Kelvin K. N. Koh,
- Cedric C. Y. Ng,
- Vikneswari Rajasegaran,
- Jolene S.M. Wong,
- Jolene S.M. Wong,
- Chin Jin Seo,
- Chin Jin Seo,
- Choon Kiat Ong,
- Choon Kiat Ong,
- Tony K. H. Lim,
- Tony K. H. Lim,
- Bin Tean Teh,
- Bin Tean Teh,
- Bin Tean Teh,
- Oi Lian Kon,
- Claramae S. Chia,
- Claramae S. Chia,
- Claramae S. Chia,
- Claramae S. Chia,
- Khee Chee Soo,
- Khee Chee Soo,
- Khee Chee Soo,
- Khee Chee Soo,
- N. Gopalakrishna Iyer,
- N. Gopalakrishna Iyer,
- N. Gopalakrishna Iyer,
- Chin-Ann J. Ong,
- Chin-Ann J. Ong,
- Chin-Ann J. Ong,
- Chin-Ann J. Ong,
- Chin-Ann J. Ong,
- Chin-Ann J. Ong
Affiliations
- Qiu Xuan Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Qiu Xuan Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Qiu Xuan Tan
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Nicholas B. Shannon
- Department of Head and Neck Surgery, Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Weng Khong Lim
- SingHealth Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore, Singapore
- Weng Khong Lim
- Cancer and Stem Biology Program, Duke-NUS Medical School, Singapore, Singapore
- Jing Xian Teo
- SingHealth Duke-NUS Institute of Precision Medicine, National Heart Centre Singapore, Singapore, Singapore
- Daniel R. Y. Yap
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Sze Min Lek
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Joey W. S. Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Joey W. S. Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Joey W. S. Tan
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Shih Jia J. Tan
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Josephine Hendrikson
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Josephine Hendrikson
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Josephine Hendrikson
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Ying Liu
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Ying Liu
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Ying Liu
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Gillian Ng
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Gillian Ng
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Gillian Ng
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Clara Y. L. Chong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Clara Y. L. Chong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Clara Y. L. Chong
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Wanyu Guo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Wanyu Guo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Wanyu Guo
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Kelvin K. N. Koh
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Cedric C. Y. Ng
- Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Vikneswari Rajasegaran
- Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Jolene S.M. Wong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Jolene S.M. Wong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Chin Jin Seo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Chin Jin Seo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Choon Kiat Ong
- Cancer and Stem Biology Program, Duke-NUS Medical School, Singapore, Singapore
- Choon Kiat Ong
- Lymphoma Genomics Translational Laboratory, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Tony K. H. Lim
- Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
- Tony K. H. Lim
- 0Pathology Academic Clinical Program, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore
- Bin Tean Teh
- Cancer and Stem Biology Program, Duke-NUS Medical School, Singapore, Singapore
- Bin Tean Teh
- Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Bin Tean Teh
- 1Institute of Molecular and Cell Biology, ASTAR Research Entities, Singapore, Singapore
- Oi Lian Kon
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Claramae S. Chia
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Claramae S. Chia
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Claramae S. Chia
- 2SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Claramae S. Chia
- 3SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Khee Chee Soo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Khee Chee Soo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Khee Chee Soo
- 2SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Khee Chee Soo
- 3SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- N. Gopalakrishna Iyer
- Department of Head and Neck Surgery, Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- N. Gopalakrishna Iyer
- Cancer and Stem Biology Program, Duke-NUS Medical School, Singapore, Singapore
- N. Gopalakrishna Iyer
- 4Cancer Therapeutics Research Laboratory, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Chin-Ann J. Ong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Chin-Ann J. Ong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Chin-Ann J. Ong
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- Chin-Ann J. Ong
- 1Institute of Molecular and Cell Biology, ASTAR Research Entities, Singapore, Singapore
- Chin-Ann J. Ong
- 2SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Chin-Ann J. Ong
- 3SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- DOI
- https://doi.org/10.3389/fonc.2024.1272432
- Journal volume & issue
-
Vol. 14
Abstract
IntroductionField cancerization is suggested to arise from imbalanced differentiation in individual basal progenitor cells leading to clonal expansion of mutant cells that eventually replace the epithelium, although without evidence.MethodsWe performed deep sequencing analyses to characterize the genomic and transcriptomic landscapes of field change in two patients with synchronous aerodigestive tract tumors.ResultsOur data support the emergence of numerous genetic alterations in cancer-associated genes but refutes the hypothesis that founder mutation(s) underpin this phenomenon. Mutational signature analysis identified defective homologous recombination as a common underlying mutational process unique to synchronous tumors.DiscussionOur analyses suggest a common etiologic factor defined by mutational signatures and/or transcriptomic convergence, which could provide a therapeutic opportunity.
Keywords
