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Evidence for etiolo...
Evidence for etiologic field changes in tongue distant from tumor in patients with squamous cell carcinoma of the oral tongue
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- Gu, Xiaolian, 1976- (författare)
- Umeå universitet,Patologi
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- Wang, Lixiao, 1975- (författare)
- Umeå universitet,Patologi
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- Coates, Philip J. (författare)
- Research Centre for Applied Molecular Oncology (RECAMO), Masaryk Memorial Cancer Institute, Brno, Czech Republic
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- Gnanasundram, Sivakumar Vadivel (författare)
- Umeå universitet,Patologi
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- Sgaramella, Nicola (författare)
- Umeå universitet,Patologi
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- Sörlin, Jonas (författare)
- Clinical Genetics, Laboratory Medicine, Norrlands Universitetssjukhus, Umeå, Sweden
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- Erdogan, Baris (författare)
- Umeå universitet,Öron- näs- och halssjukdomar
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- Magan, Mustafa (författare)
- Umeå universitet,Öron- näs- och halssjukdomar
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- Nylander, Karin (författare)
- Umeå universitet,Patologi
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(creator_code:org_t)
- 2022-12-05
- 2023
- Engelska.
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 259:1, s. 93-102
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Oral cancer is a paradigm of Slaughter's concept of field cancerization, where tumors are thought to originate within an area of cells containing genetic alterations that predispose to cancer development. The field size is unclear but may represent a large area of tissue, and the origin of mutations is also unclear. Here, we analyzed whole exome and transcriptome features in contralateral tumor-distal tongue (i.e. distant from the tumor, not tumor-adjacent) and corresponding tumor tissues of 15 patients with squamous cell carcinoma of the oral tongue. The number of point mutations ranged from 41 to 237 in tumors and from one to 78 in tumor-distal samples. Tumor-distal samples showed mainly clock-like (associated with aging) or tobacco smoking mutational signatures. Tumors additionally showed mutations that associate with cytidine deaminase AID/APOBEC enzyme activities or a UV-like signature. Importantly, no point mutations were shared between a tumor and the matched tumor-distal sample in any patient. TP53 was the most frequently mutated gene in tumors (67%), whereas a TP53 mutation was detected in only one tumor-distal sample, and this mutation was not shared with the matched tumor. Arm-level copy number variation (CNV) was found in 12 tumors, with loss of chromosome (Chr) 8p or gain of 8q being the most frequent events. Two tumor-distal samples showed a gain of Chr8, which was associated with increased expression of Chr8-located genes in these samples, although gene ontology did not show a role for these genes in oncogenic processes. In situ hybridization revealed a mixed pattern of Chr8 gain and neutral copy number in both tumor cells and adjacent nontumor epithelium in one patient. We conclude that distant field cancerization exists but does not present as tumor-related mutational events. The data are compatible with etiologic field effects, rather than classical monoclonal field cancerization theory. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- chromosome 8
- CNV
- field cancerization
- SCCOT
- SNV
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Gu, Xiaolian, 19 ...
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Wang, Lixiao, 19 ...
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Coates, Philip J ...
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Gnanasundram, Si ...
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Sgaramella, Nico ...
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Sörlin, Jonas
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Erdogan, Baris
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Magan, Mustafa
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Nylander, Karin
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- MEDICIN OCH HÄLSOVETENSKAP
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och Klinisk medicin
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Journal of Patho ...
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Umeå universitet